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Luo Q, Xu T, Ainiwaer Z, Fan W, Wang C. Effect of biotin on growth performance, serum biochemical profiles, and histomorphological changes in acetate gossypol-treated mice. Front Vet Sci 2025; 12:1562325. [PMID: 40303386 PMCID: PMC12037636 DOI: 10.3389/fvets.2025.1562325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 03/28/2025] [Indexed: 05/02/2025] Open
Abstract
The objective of this study was to determine the effects of biotin on growth performance, serum biochemical profiles, and morphology of acetate gossypol-treated mice. Seventy-five healthy male Kunming mice were randomly assigned to five treatment groups: the control group (C), the biotin control group (BC), the acetate gossypol control group (AGC), the biotin prevention group (BP) and the biotin treatment group (BT). The study examined the growth performance, visceral index, serum biochemical profiles and histomorphological changes of mice. The results showed that compared with AGC group mice, the average daily feed intake of BP group and BT group increased by 40.47 and 45.69% (p < 0.05). Biotin prevention reduced the elevated blood urea nitrogen (BUN) levels in acetate gossypol-treated mice, biotin treatment reduced the elevated serum aspartate aminotransferase (AST), total protein (TP) and BUN levels in acetate gossypol-treated mice (p < 0.05). Biotin increase the values of villus height/crypt depth in duodenum and jejunum (p < 0.05). In conclusion, biotin potentially increase the growth performance of acetate gossypol-treated mice, it also has a positive effect on serum biochemical profiles, and histomorphological of acetate gossypol-treated mice.
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Affiliation(s)
- Qiyu Luo
- College of Animal Sciences, Xinjiang Agricultural University, Urumqi, China
- Xinjiang Key Laboratory of Herbivore Nutrition for Meat and Milk, Urumqi, China
- Research Center for Biofeed and Animal Gut Health, Urumqi, China
| | - Tongxiang Xu
- College of Animal Sciences, Xinjiang Agricultural University, Urumqi, China
- Xinjiang Key Laboratory of Herbivore Nutrition for Meat and Milk, Urumqi, China
- Research Center for Biofeed and Animal Gut Health, Urumqi, China
| | - Zulibina Ainiwaer
- College of Animal Sciences, Xinjiang Agricultural University, Urumqi, China
- Xinjiang Key Laboratory of Herbivore Nutrition for Meat and Milk, Urumqi, China
- Research Center for Biofeed and Animal Gut Health, Urumqi, China
| | - Wenpeng Fan
- College of Animal Sciences, Xinjiang Agricultural University, Urumqi, China
- Xinjiang Key Laboratory of Herbivore Nutrition for Meat and Milk, Urumqi, China
- Research Center for Biofeed and Animal Gut Health, Urumqi, China
| | - Caidie Wang
- College of Animal Sciences, Xinjiang Agricultural University, Urumqi, China
- Xinjiang Key Laboratory of Herbivore Nutrition for Meat and Milk, Urumqi, China
- Research Center for Biofeed and Animal Gut Health, Urumqi, China
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Sakurai-Yageta M, Suzuki Y. Molecular Mechanisms of Biotin in Modulating Inflammatory Diseases. Nutrients 2024; 16:2444. [PMID: 39125325 PMCID: PMC11314543 DOI: 10.3390/nu16152444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin and serves as an essential co-enzyme for five specific carboxylases. Holocarboxylase synthase (HCS) activates biotin and facilitates its covalent attachment to these enzymes, while biotinidase releases free biotin in the biotin cycle. The transport of biotin, primarily from the intestine, is mediated by the sodium-dependent multi-vitamin transporter (SMVT). Severe biotin deficiency leads to multiple carboxylase deficiency. Moreover, biotin is crucial to glucose and lipid utilization in cellular energy production because it modulates the expression of metabolic enzymes via various signaling pathways and transcription factors. Biotin also modulates the production of proinflammatory cytokines in the immune system through similar molecular mechanisms. These regulatory roles in metabolic and immune homeostasis connect biotin to conditions such as diabetes, dermatologic manifestations, and multiple sclerosis. Furthermore, deficiencies in biotin and SMVT are implicated in inflammatory bowel disease, affecting intestinal inflammation, permeability, and flora. Notably, HCS and probably biotin directly influence gene expression through histone modification. In this review, we summarize the current knowledge on the molecular aspects of biotin and associated molecules in diseases related to both acute inflammatory responses and chronic inflammation, and discuss the potential therapeutic applications of biotin.
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Affiliation(s)
- Mika Sakurai-Yageta
- Department of Education and Training, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Miyagi, Japan
- Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai 980-8573, Miyagi, Japan
| | - Yoichi Suzuki
- Department of Education and Training, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Miyagi, Japan
- Department of Clinical Genetics, Ageo Central General Hospital, Ageo 362-8588, Saitama, Japan
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Moaness M, Kamel AM, Salama A, Kamel R, Beherei HH, Mabrouk M. Fast skin healing chitosan/PEO hydrogels: In vitro and in vivo studies. Int J Biol Macromol 2024; 265:130950. [PMID: 38513911 DOI: 10.1016/j.ijbiomac.2024.130950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 03/04/2024] [Accepted: 03/15/2024] [Indexed: 03/23/2024]
Abstract
Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1β, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-β and increasing ECM synthesis as it elevates collagen 1 and α-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.
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Affiliation(s)
- Mona Moaness
- Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt.
| | - Amira M Kamel
- Polymers and Pigments Department, National Research Centre, 33El Bohouth St., Dokki, PO Box12622, Cairo, Egypt
| | - Abeer Salama
- Pharmacology Department National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| | - Rabab Kamel
- Pharmaceutical Technology Department, National Research Centre, Dokki, 12622 Cairo, Egypt
| | - Hanan H Beherei
- Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
| | - Mostafa Mabrouk
- Refractories, Ceramics and Building Materials Department, Advanced Materials Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt
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Wang Y, He X, Xue M, Yu H, He Q, Jin J. Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice. Acta Biochim Biophys Sin (Shanghai) 2024; 56:414-426. [PMID: 38429975 PMCID: PMC10984863 DOI: 10.3724/abbs.2024021] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/03/2023] [Indexed: 03/03/2024] Open
Abstract
Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.
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Affiliation(s)
- Yunguang Wang
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Xinxin He
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Mengjiao Xue
- School of Clinical MedicineHangzhou Medical CollegeHangzhou311399China
| | - Huan Yu
- The Fourth Clinical Medical CollegeZhejiang Chinese Medical UniversityHangzhou310053China
| | - Qiang He
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
| | - Juan Jin
- Department of Nephrologythe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)Hangzhou310006China
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Liu H, Lin Y, Chen X, Yang G. Effects of rumen-protected biotin on the growth performance, nitrogen utilization and blood parameters of yearling Liaoning cashmere doelings. Anim Biosci 2023; 36:1685-1692. [PMID: 37641838 PMCID: PMC10623043 DOI: 10.5713/ab.23.0078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/08/2023] [Accepted: 07/14/2023] [Indexed: 08/31/2023] Open
Abstract
OBJECTIVE This study was conducted to investigate the effects of rumen-protected biotin (RPB) on growth performance, nutrient digestibility, nitrogen utilization and plasma biochemical parameters of Liaoning cashmere goats during the cashmere fiber growing period. METHODS Sixteen 6-month-old Liaoning cashmere twin-doelings (24.8±1.20 kg) were allocated to 2 diet groups that were individually ad libitum fed 30% concentrate and 70% forage diet (dry matter [DM]) by a paired experimental design. Goats of the control group were fed the basal diet, while goats belonging to the RPB group were fed the basal diet with 10 mg RPB/d per animal. The duration of the experiment was 16 weeks with two 8-week periods. Digestibility was determined at weeks 7 and 15, and other measures were taken every four weeks. RESULTS Compared with the control group, the average daily gain of the RPB group increased by 10.94% (p<0.05), and the intake of neutral detergent fiber was increased (p = 0.045). There were some increasing tendencies for the intake of DM, acid detergent fiber and ether extract (p = 0.070, 0.088, and 0.070, respectively). The intake and digestibility of N tended to increase (p = 0.062 and 0.093, respectively), while the N fecal excretion percentage of N intake was decreased (p = 0.093) in the RPB compared with the control group. N retention tended to increase (p = 0.084) with the addition of adding RPB to the diet. Plasma total protein was increased (p = 0.037), whereas the urea-N concentration was decreased (p = 0.049) in the RPB diet group compared with the control diet group. The levels of propionyl-CoA carboxylase (p<0.001) and methylmalonyl-CoA (p = 0.013) were increased in the RPB group. CONCLUSION Supplementation of rumen-protected biotin in the diet of cashmere goats can enhance the utilization of N and improve daily weight gain during cashmere fiber growing period.
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Affiliation(s)
- Haiying Liu
- College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866,
China
| | - Ying Lin
- College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866,
China
| | - Xuhui Chen
- College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866,
China
| | - Guiqin Yang
- College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866,
China
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Li K, Chen Y, Xie J, Cai W, Pang C, Cui C, Huan Y, Deng B. How vitamins act as novel agents for ameliorating diabetic peripheral neuropathy: A comprehensive overview. Ageing Res Rev 2023; 91:102064. [PMID: 37689144 DOI: 10.1016/j.arr.2023.102064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 08/10/2023] [Accepted: 09/01/2023] [Indexed: 09/11/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is a pervasive and incapacitating sequela of diabetes, affecting a significant proportion of those diagnosed with the disease, yet an effective treatment remains elusive. Vitamins have been extensively studied, emerging as a promising target for diagnosing and treating various systemic diseases, but their role in DPN is not known. This review collates and synthesizes knowledge regarding the interplay between vitamins and DPN, drawing on bibliographies from prior studies and relevant articles, and stratifying the therapeutic strategies from prophylactic to interventional. In addition, the clinical evidence supporting the use of vitamins to ameliorate DPN is also evaluated, underscoring the potential of vitamins as putative therapeutic agents. We anticipate that this review will offer novel insights for developing and applying vitamin-based therapies for DPN.
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Affiliation(s)
- Kezheng Li
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China
| | - Yinuo Chen
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China
| | - Jiali Xie
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China
| | - Weiwei Cai
- Department of Rheumatology and Immunology, Beijing Hospital, Beijing, PR China
| | - Chunyang Pang
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China
| | - Can Cui
- Department of Clinical Sciences Malmö, Lund University, Skåne, Sweden
| | - Yu Huan
- Department of Pediatrics, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, PR China
| | - Binbin Deng
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China.
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Iloki Assanga SB, Lewis Luján LM, McCarty MF. Targeting beta-catenin signaling for prevention of colorectal cancer - Nutraceutical, drug, and dietary options. Eur J Pharmacol 2023; 956:175898. [PMID: 37481200 DOI: 10.1016/j.ejphar.2023.175898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 06/09/2023] [Accepted: 06/29/2023] [Indexed: 07/24/2023]
Abstract
Progressive up-regulation of β-catenin signaling is very common in the transformation of colorectal epithelium to colorectal cancer (CRC). Practical measures for opposing such signaling hence have potential for preventing or slowing such transformation. cAMP/PKA activity in colon epithelium, as stimulated by COX-2-generated prostaglandins and β2-adrenergic signaling, boosts β-catenin activity, whereas cGMP/PKG signaling has the opposite effect. Bacterial generation of short-chain fatty acids (as supported by unrefined high-carbohydrate diets, berberine, and probiotics), dietary calcium, daily aspirin, antioxidants opposing cox-2 induction, and nicotine avoidance, can suppress cAMP production in colonic epithelium, whereas cGMP can be boosted via linaclotides, PDE5 inhibitors such as sildenafil or icariin, and likely high-dose biotin. Selective activation of estrogen receptor-β by soy isoflavones, support of adequate vitamin D receptor activity with UV exposure or supplemental vitamin D, and inhibition of CK2 activity with flavanols such as quercetin, can also oppose β-catenin signaling in colorectal epithelium. Secondary bile acids, the colonic production of which can be diminished by low-fat diets and berberine, can up-regulate β-catenin activity by down-regulating farnesoid X receptor expression. Stimulation of PI3K/Akt via insulin, IGF-I, TLR4, and EGFR receptors boosts β-catenin levels via inhibition of glycogen synthase-3β; plant-based diets can down-regulate insulin and IGF-I levels, exercise training and leanness can keep insulin low, anthocyanins and their key metabolite ferulic acid have potential for opposing TLR4 signaling, and silibinin is a direct antagonist for EGFR. Partially hydrolyzed phytate can oppose growth factor-mediated down-regulation of β-catenin by inhibiting Akt activation. Multifactorial strategies for safely opposing β-catenin signaling can be complemented with measures that diminish colonic mutagenesis and DNA hypomethylation - such as avoidance of heme-rich meat and charred or processed meats, consumption of phase II-inductive foods and nutraceuticals (e.g., Crucifera), and assurance of adequate folate status.
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Affiliation(s)
- Simon Bernard Iloki Assanga
- Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Blvd Luis Encinas y Rosales S/N Col. Centro, Hermosillo, Sonora, C.P. 83000, Mexico.
| | - Lidianys María Lewis Luján
- Technological Institute of Hermosillo (ITH), Ave. Tecnológico y Periférico Poniente S/N, Col. Sahuaro, Hermosillo, Sonora, C.P. 83170, México.
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Wu HHL, McDonnell T, Chinnadurai R. Physiological Associations between Vitamin B Deficiency and Diabetic Kidney Disease. Biomedicines 2023; 11:biomedicines11041153. [PMID: 37189771 DOI: 10.3390/biomedicines11041153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/24/2023] [Accepted: 04/10/2023] [Indexed: 05/17/2023] Open
Abstract
The number of people living with chronic kidney disease (CKD) is growing as our global population continues to expand. With aging, diabetes, and cardiovascular disease being major harbingers of kidney disease, the number of people diagnosed with diabetic kidney disease (DKD) has grown concurrently. Poor clinical outcomes in DKD could be influenced by an array of factors-inadequate glycemic control, obesity, metabolic acidosis, anemia, cellular senescence, infection and inflammation, cognitive impairment, reduced physical exercise threshold, and, importantly, malnutrition contributing to protein-energy wasting, sarcopenia, and frailty. Amongst the various causes of malnutrition in DKD, the metabolic mechanisms of vitamin B (B1 (Thiamine), B2 (Riboflavin), B3 (Niacin/Nicotinamide), B5 (Pantothenic Acid), B6 (Pyridoxine), B8 (Biotin), B9 (Folate), and B12 (Cobalamin)) deficiency and its clinical impact has garnered greater scientific interest over the past decade. There remains extensive debate on the biochemical intricacies of vitamin B metabolic pathways and how their deficiencies may affect the development of CKD, diabetes, and subsequently DKD, and vice-versa. Our article provides a review of updated evidence on the biochemical and physiological properties of the vitamin B sub-forms in normal states, and how vitamin B deficiency and defects in their metabolic pathways may influence CKD/DKD pathophysiology, and in reverse how CKD/DKD progression may affect vitamin B metabolism. We hope our article increases awareness of vitamin B deficiency in DKD and the complex physiological associations that exist between vitamin B deficiency, diabetes, and CKD. Further research efforts are needed going forward to address the knowledge gaps on this topic.
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Affiliation(s)
- Henry H L Wu
- Renal Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, NSW 2065, Australia
| | - Thomas McDonnell
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK
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Nam YH, Kim EB, Kang JE, Kim JS, Jeon Y, Shin SW, Kang TH, Kwak JH. Ameliorative Effects of Flavonoids from Platycodon grandiflorus Aerial Parts on Alloxan-Induced Pancreatic Islet Damage in Zebrafish. Nutrients 2023; 15:nu15071798. [PMID: 37049638 PMCID: PMC10096680 DOI: 10.3390/nu15071798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/03/2023] [Accepted: 04/04/2023] [Indexed: 04/14/2023] Open
Abstract
Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (1-8) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (1) and II (2), were elucidated to be luteolin 7-O-α-L-rhamno-pyranosyl (1 → 2)-(6-O-acetyl)-β-D-glucopyranoside and apigenin 7-O-α-L-rhamnopyranosyl (1 → 2)-(6-O-acetyl)-β-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 6-8 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked KATP channels in pancreatic β-cells. Furthermore, compounds 3, 4, 6 and 7 showed significant changes with respect to the mRNA expression of GCK, GCKR, GLIS3 and CDKN2B compared to alloxan-induced zebrafish. In conclusion, the aerial part of P. grandiflorus and its constituents conferred a regenerative effect on injured pancreatic islets.
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Affiliation(s)
- Youn Hee Nam
- Department of Oriental Medicine Biotechnology, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Global Campus, Yongin 17104, Republic of Korea
| | - Eun Bin Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ji Eun Kang
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ju Su Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Yukyoung Jeon
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Sung Woo Shin
- Department of Oriental Medicine Biotechnology, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Global Campus, Yongin 17104, Republic of Korea
| | - Tong Ho Kang
- Department of Oriental Medicine Biotechnology, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Global Campus, Yongin 17104, Republic of Korea
| | - Jong Hwan Kwak
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
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Morales-Reyes I, Atwater I, Esparza-Aguilar M, Pérez-Armendariz EM. Impact of biotin supplemented diet on mouse pancreatic islet β-cell mass expansion and glucose induced electrical activity. Islets 2022; 14:149-163. [PMID: 35758027 PMCID: PMC9733685 DOI: 10.1080/19382014.2022.2091886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
Biotin supplemented diet (BSD) is known to enhance β-cell replication and insulin secretion in mice. Here, we first describe BSD impact on the islet β-cell membrane potential (Vm) and glucose-induced electrical activity. BALB/c female mice (n ≥ 20) were fed for nine weeks after weaning with a control diet (CD) or a BSD (100X). In both groups, islet area was compared in pancreatic sections incubated with anti-insulin and anti-glucagon antibodies; Vm was recorded in micro dissected islet β-cells during perfusion with saline solutions containing 2.8, 5.0, 7.5-, or 11.0 mM glucose. BSD increased the islet and β-cell area compared with CD. In islet β-cells of the BSD group, a larger ΔVm/Δ[glucose] was found at sub-stimulatory glucose concentrations and the threshold glucose concentration for generation of action potentials (APs) was increased by 1.23 mM. Moreover, at 11.0 mM glucose, a significant decrease was found in AP amplitude, frequency, ascending and descending slopes as well as in the calculated net charge influx and efflux of islet β-cells from BSD compared to the CD group, without changes in slow Vm oscillation parameters. A pharmacological dose of biotin in mice increases islet insulin cell mass, shifts islet β-cell intracellular electrical activity dose response curve toward higher glucose concentrations, very likely by increasing KATP conductance, and decreases voltage gated Ca2+ and K+ conductance at stimulatory glucose concentrations.
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Affiliation(s)
- Israel Morales-Reyes
- Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Circuito Interior S/N, Universidad Nacional Autónoma de México, C.U., CDMXLaboratorio de sinapsis eléctricas. Departamento de Biología Celular y , México
| | - Illani Atwater
- Human Genetics Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Marcelino Esparza-Aguilar
- Unidad de Investigación en Epidemiología, Instituto Nacional de Pediatría, México. Ciudad de México, México
| | - E. Martha Pérez-Armendariz
- Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Circuito Interior S/N, Universidad Nacional Autónoma de México, C.U., CDMXLaboratorio de sinapsis eléctricas. Departamento de Biología Celular y , México
- CONTACT E. Martha Pérez-Armendariz ; Laboratorio de sinapsis eléctricas. Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Circuito Interior S/N, Universidad Nacional Autónoma de México, C.U., CDMX, C.P. 04510, México
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Łoniewski I, Szulińska M, Kaczmarczyk M, Podsiadło K, Styburski D, Skonieczna-Żydecka K, Bogdański P. Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study. J Transl Med 2022; 20:585. [PMID: 36503483 PMCID: PMC9743526 DOI: 10.1186/s12967-022-03801-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 12/01/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Microbiota and its metabolites are known to regulate host metabolism. In cross-sectional study conducted in postmenopausal women we aimed to assess whether the microbiota, its metabolites and gut barrier integrity marker are correlated with cardiometabolic risk factors and if microbiota is different between obese and non-obese subjects. METHODS We analysed the faecal microbiota of 56 obese, postmenopausal women by means of 16S rRNA analysis. Stool short chain fatty acids, calprotectin and anthropometric, physiological and biochemical parameters were correlates to microbiome analyses. RESULTS Alpha-diversity was inversely correlated with lipopolysaccharide (Rho = - 0.43, FDR P (Q) = 0.004). Bray-Curtis distance based RDA revealed that visceral fat and waist circumference had a significant impact on metabolic potential (P = 0.003). Plasma glucose was positively correlated with the Coriobacteriaceae (Rho = 0.48, Q = 0.004) and its higher taxonomic ranks, up to phylum (Actinobacteria, Rho = 0.46, Q = 0.004). At the metabolic level, the strongest correlation was observed for the visceral fat (Q < 0.15), especially with the DENOVOPURINE2-PWY, PWY-841 and PWY0-162 pathways. Bacterial abundance was correlated with SCFAs, thus some microbiota-glucose relationships may be mediated by propionate, as indicated by the significant average causal mediation effect (ACME): Lachnospiraceae (ACME 1.25, 95%CI (0.10, 2.97), Firmicutes (ACME 1.28, 95%CI (0.23, 3.83)) and Tenericutes (ACME - 0.39, 95%CI (- 0.87, - 0.03)). There were significant differences in the distribution of phyla between this study and Qiita database (P < 0.0001). CONCLUSIONS Microbiota composition and metabolic potential are associated with some CMRF and fecal SCFAs concentration in obese postmenopausal women. There is no unequivocal relationship between fecal SCFAs and the marker of intestinal barrier integrity and CMRF. Further studies with appropriately matched control groups are warranted to look for causality between SCFAs and CMRF.
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Affiliation(s)
- Igor Łoniewski
- grid.107950.a0000 0001 1411 4349Department of Biochemical Sciences, Pomeranian Medical University in Szczecin, Broniewskiego 24, 71-460 Szczecin, Poland ,Department of Human Nutrition and Metabolomics, Broniewskiego 24, 71-460 Szczecin, Poland ,Sanprobi Sp. Z O. O. Sp. K., Kurza Stopka 5/C, 70-535 Szczecin, Poland
| | - Monika Szulińska
- grid.22254.330000 0001 2205 0971Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences in Poznań, Szamarzewskiego Str. 84, 60-569 Poznań, Poland
| | - Mariusz Kaczmarczyk
- Sanprobi Sp. Z O. O. Sp. K., Kurza Stopka 5/C, 70-535 Szczecin, Poland ,grid.107950.a0000 0001 1411 4349Department of Clinical Biochemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
| | - Konrad Podsiadło
- Sanprobi Sp. Z O. O. Sp. K., Kurza Stopka 5/C, 70-535 Szczecin, Poland
| | - Daniel Styburski
- Sanprobi Sp. Z O. O. Sp. K., Kurza Stopka 5/C, 70-535 Szczecin, Poland
| | - Karolina Skonieczna-Żydecka
- grid.107950.a0000 0001 1411 4349Department of Biochemical Sciences, Pomeranian Medical University in Szczecin, Broniewskiego 24, 71-460 Szczecin, Poland
| | - Paweł Bogdański
- grid.22254.330000 0001 2205 0971Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences in Poznań, Szamarzewskiego Str. 84, 60-569 Poznań, Poland
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12
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Belda E, Voland L, Tremaroli V, Falony G, Adriouch S, Assmann KE, Prifti E, Aron-Wisnewsky J, Debédat J, Le Roy T, Nielsen T, Amouyal C, André S, Andreelli F, Blüher M, Chakaroun R, Chilloux J, Coelho LP, Dao MC, Das P, Fellahi S, Forslund S, Galleron N, Hansen TH, Holmes B, Ji B, Krogh Pedersen H, Le P, Le Chatelier E, Lewinter C, Mannerås-Holm L, Marquet F, Myridakis A, Pelloux V, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Sokolovska N, Søndertoft NB, Touch S, Vieira-Silva S, The MetaCardis Consortium, Galan P, Holst J, Gøtze JP, Køber L, Vestergaard H, Hansen T, Hercberg S, Oppert JM, Nielsen J, Letunic I, Dumas ME, Stumvoll M, Pedersen OB, Bork P, Ehrlich SD, Zucker JD, Bäckhed F, Raes J, Clément K. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism. Gut 2022; 71:2463-2480. [PMID: 35017197 PMCID: PMC9664128 DOI: 10.1136/gutjnl-2021-325753] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 12/15/2021] [Indexed: 01/08/2023]
Abstract
OBJECTIVES Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER NCT02059538.
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Affiliation(s)
- Eugeni Belda
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France,Integrative Phenomics, Paris, France
| | - Lise Voland
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Valentina Tremaroli
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden
| | - Gwen Falony
- Center for Microbiology, VIB, Leuven, Belgium,Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium
| | - Solia Adriouch
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Karen E Assmann
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Edi Prifti
- Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France
| | - Judith Aron-Wisnewsky
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France,Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France
| | - Jean Debédat
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Tiphaine Le Roy
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Trine Nielsen
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Chloé Amouyal
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Sébastien André
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Fabrizio Andreelli
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Matthias Blüher
- Medical Department III - Endocrinology, Nephrology, Rheumatology - Medical Center, Faculty of Medicine, University of Leipzig, Leipzig, Germany
| | - Rima Chakaroun
- Medical Department III - Endocrinology, Nephrology, Rheumatology - Medical Center, Faculty of Medicine, University of Leipzig, Leipzig, Germany
| | - Julien Chilloux
- Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London Faculty of Medicine, London, UK
| | - Luis Pedro Coelho
- Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany,Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Maria Carlota Dao
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Promi Das
- Department of Biology, Chalmers University of Technology, Goteborg, Sweden
| | - Soraya Fellahi
- Functional Unit, Biochemistry and Hormonology Department, enon Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France,Saint-Antoine Research Center, Sorbonne Université, INSERM, Paris, France
| | - Sofia Forslund
- Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, Germany
| | - Nathalie Galleron
- MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Tue H Hansen
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Bridget Holmes
- Centre Daniel Carasso, Global Nutrition Department, Danone Nutricia Research, Palaiseau, France
| | - Boyang Ji
- Department of Biology, Chalmers University of Technology, Goteborg, Sweden
| | - Helle Krogh Pedersen
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Phuong Le
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | | | | | - Louise Mannerås-Holm
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden
| | - Florian Marquet
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Antonis Myridakis
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Veronique Pelloux
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Nicolas Pons
- MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Benoit Quinquis
- MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Christine Rouault
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Hugo Roume
- MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France
| | - Joe-Elie Salem
- Department of Pharmacology and CIC-1421, Assistance Publique-Hôpitaux de Paris, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
| | - Nataliya Sokolovska
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Nadja B Søndertoft
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Sothea Touch
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France
| | - Sara Vieira-Silva
- Center for Microbiology, VIB, Leuven, Belgium,Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium
| | | | - Pilar Galan
- Nutritional Epidemiology Unit, INSERM, INRAE, CNAM, Paris 13 University, Bobigny, France
| | - Jens Holst
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Jens Peter Gøtze
- Department of Clinical Biochemistry, Rigshospitalet, Kobenhavn, Denmark
| | - Lars Køber
- Department of Cardiology, Rigshospitalet, Kobenhavn, Denmark
| | - Henrik Vestergaard
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark,Steno Diabetes Center, Copenhagen, Gentofte, Denmark
| | - Torben Hansen
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark,Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Serge Hercberg
- Nutritional Epidemiology Unit, INSERM, INRAE, CNAM, Paris 13 University, Bobigny, France
| | - Jean-Michel Oppert
- Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France
| | - Jens Nielsen
- Department of Biology, Chalmers University of Technology, Goteborg, Sweden
| | | | - Marc-Emmanuel Dumas
- Department of Surgery and Cancer, Section of Computational and Systems Medicine, Imperial College London, London, UK,National Heart & Lung Institute, Section of Genomic & Environmental Medicine, Imperial College London, London, UK
| | - Michael Stumvoll
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München, University of Leipzig Faculty of Medicine, Leipzig, Germany
| | - Oluf Borbye Pedersen
- Center for Basic Metabolic Research, Novo Nordisk Foundation, University of Copenhagen, Kobenhavn, Denmark
| | - Peer Bork
- Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany,Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Stanislav Dusko Ehrlich
- MetaGenoPolis, Université Paris-Saclay, INRAE, Jouy-en-Josas, France,Center for Host Microbiome Interactions, King's College London Dental Institute, London, UK
| | - Jean-Daniel Zucker
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France,Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, UMMISCO, Sorbonne Université, IRD, Bondy, France
| | - Fredrik Bäckhed
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Goteborg, Sweden
| | - Jeroen Raes
- Center for Microbiology, VIB, Leuven, Belgium,Vlaams Instituut voor Biotechnologie, VIB-KU Leuven, Heverlee, Flanders, Belgium
| | - Karine Clément
- Nutrition and Obesities: Systemic Approaches, NutriOmics, Research Unit, Sorbonne Université, INSERM, Paris, France .,Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique - Hopitaux de Paris, Paris, France
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13
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Zhang Y, Ding Y, Fan Y, Xu Y, Lu Y, Zhai L, Wang L. Influence of biotin intervention on glycemic control and lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Front Nutr 2022; 9:1046800. [PMID: 36386951 PMCID: PMC9659605 DOI: 10.3389/fnut.2022.1046800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Accepted: 10/17/2022] [Indexed: 08/09/2023] Open
Abstract
Background Biotin is a water-soluble vitamin acting as a covalently bound coenzyme in regulating energy production. Previous studies have reported that biotin supplementation may influence blood glucose and lipid level in patients with type 2 diabetes mellitus (T2DM). Methods We searched Pubmed, Embase, and Cochrane library databases up to 8th August 2022 for studies examining the effects of biotin supplementation in T2DM patients. Pooled effects were measured by weighted mean differences (WMDs) with 95% confidence intervals (CI) using random effects models. Inter-study heterogeneity was assessed and quantified. Results A total of five random controlled trials (RCT), involving 445 participants were included. It was suggested that biotin supplementation for 28 to 90 days significantly decreased the level of fasting blood glucose (FBG) (MD: -1.21 mmol/L, 95% CI: -2.73 to 0.31), total cholesterol (TC) (MD: -0.22 mmol/L, 95% CI: -0.25 to -0.19) and triglycerides (TG) (MD: -0.59 mmol/L, 95% CI: -1.21 to 0.03). No significant beneficial effects were observed on insulin (MD: 1.88 pmol/L 95% CI: -13.44 to 17.21). Evidence for the impact of biotin supplementation on the levels of glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C) was limited to draw conclusion. Conclusions Biotin supplementation may decrease FBG, TC and TG levels. However, its influence on insulin is not significant and further studies on the effects of biotin on HbA1c, LDL-C, HDL-C and VLDL-C are expected.
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Affiliation(s)
| | | | | | | | | | | | - Ling Wang
- Faculty of Medicine, Macau University of Science and Technology, Macao, Macao SAR, China
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14
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Abstract
Purpose The reference values for biotin intake for Germany, Austria and Switzerland lead back to a report in 2000. Following a timely update process, they were revised in 2020. Methods For infants aged 0 to < 4 months, adequate biotin supply via human milk was assumed and in consequence the reference value reflects the amount of biotin delivered by human milk. For infants aged 4 to < 12 months, biotin intake was extrapolated from the reference value for younger infants. Due to missing data on average requirement, the reference values for biotin intake for children, adolescents and adults were derived based on observed intake levels. The reference value for lactating women considered in addition biotin losses via human milk. Results The reference value for biotin intake for infants aged 0 to < 4 months was set at 4 µg/day and for infants aged 4 to < 12 months at 6 µg/day. In children and adolescents, the reference values for biotin intake ranged from 20 µg/day in children 1 to < 4 years to 40 µg/day in youths 15 to < 19 years. For adults including pregnant women, 40 µg/day was derived as reference value for biotin intake. For lactating women, this value was set at 45 µg/day. Conclusions As deficiency symptoms of biotin do not occur with a usual mixed diet and the average requirement cannot be determined, reference values for an adequate biotin intake for populations from Germany, Austria and Switzerland were derived from biotin intake levels assessed in population-based nutrition surveys. Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02756-0.
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McCarty MF, DiNicolantonio JJ. Maintaining Effective Beta Cell Function in the Face of Metabolic Syndrome-Associated Glucolipotoxicity-Nutraceutical Options. Healthcare (Basel) 2021; 10:3. [PMID: 35052168 PMCID: PMC8775473 DOI: 10.3390/healthcare10010003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 11/16/2022] Open
Abstract
In people with metabolic syndrome, episodic exposure of pancreatic beta cells to elevated levels of both glucose and free fatty acids (FFAs)-or glucolipotoxicity-can induce a loss of glucose-stimulated insulin secretion (GSIS). This in turn can lead to a chronic state of glucolipotoxicity and a sustained loss of GSIS, ushering in type 2 diabetes. Loss of GSIS reflects a decline in beta cell glucokinase (GK) expression associated with decreased nuclear levels of the pancreatic and duodenal homeobox 1 (PDX1) factor that drives its transcription, along with that of Glut2 and insulin. Glucolipotoxicity-induced production of reactive oxygen species (ROS), stemming from both mitochondria and the NOX2 isoform of NADPH oxidase, drives an increase in c-Jun N-terminal kinase (JNK) activity that promotes nuclear export of PDX1, and impairs autocrine insulin signaling; the latter effect decreases PDX1 expression at the transcriptional level and up-regulates beta cell apoptosis. Conversely, the incretin hormone glucagon-like peptide-1 (GLP-1) promotes nuclear import of PDX1 via cAMP signaling. Nutraceuticals that quell an increase in beta cell ROS production, that amplify or mimic autocrine insulin signaling, or that boost GLP-1 production, should help to maintain GSIS and suppress beta cell apoptosis in the face of glucolipotoxicity, postponing or preventing onset of type 2 diabetes. Nutraceuticals with potential in this regard include the following: phycocyanobilin-an inhibitor of NOX2; agents promoting mitophagy and mitochondrial biogenesis, such as ferulic acid, lipoic acid, melatonin, berberine, and astaxanthin; myo-inositol and high-dose biotin, which promote phosphatidylinositol 3-kinase (PI3K)/Akt activation; and prebiotics/probiotics capable of boosting GLP-1 secretion. Complex supplements or functional foods providing a selection of these agents might be useful for diabetes prevention.
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Affiliation(s)
| | - James J. DiNicolantonio
- Department of Preventive Cardiology, Saint Luke’s Mid America Heart Institute, Kansas City, MO 64111, USA
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Salazar-Anzures T, Pastén-Hidalgo K, Sicilia-Argumedo G, Riverón-Negrete L, Hernández-Vázquez ADJ, Fernanadez-Mejia C. Dietary biotin supplementation increases proliferation pathways in mice testes without affecting serum follicle-stimulating hormone levels and stem cell factor expression. Toxicol Appl Pharmacol 2021; 433:115774. [PMID: 34699867 DOI: 10.1016/j.taap.2021.115774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 10/17/2021] [Accepted: 10/19/2021] [Indexed: 11/18/2022]
Abstract
Supplements containing pharmacological concentrations of biotin are commercially available. The mechanisms by which biotin at pharmacological concentrations exerts its action have been the subject of multiple investigations, particularly for biotin's medicinal potential and wide use for cosmetic purposes. Several studies have reported that biotin supplementation increases cell proliferation; however, the mechanisms involved in this effect have not yet been characterized. In a previous study, we found that a biotin-supplemented diet increased spermatogonia proliferation. The present study was focused on investigating the molecular mechanisms involved in biotin-induced testis cell proliferation. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for eight weeks. Compared with the control group, the biotin-supplemented mice presented augmented protein abundance of the c-kit-receptor and pERK1/2Tyr204 and pAKTSer473, the active forms of ERK/AKT proliferation signaling pathways. No changes were observed in the testis expression of the stem cell factor and in the serum levels of the follicle-stimulating hormone. Analysis of mRNA abundance found an increase in cyclins Ccnd3, Ccne1, Ccna2; Kinases Cdk4, Cdk2; and E2F; and Sp1 & Sp3 transcription factors. Decreased expression of cyclin-dependent kinase inhibitor 1a (p21) was observed but not of Cdkn2a inhibitor (p16). The results of the present study identifies, for the first time, the mechanisms associated with biotin supplementation-induced cell proliferation, which raises concerns about the effects of biotin on male reproductive health because of its capacity to cause hyperplasia, especially because this vitamin is available in large amounts without regulation.
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Affiliation(s)
- Tonatiuh Salazar-Anzures
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico
| | - Karina Pastén-Hidalgo
- Cátedra CONACYT, Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico
| | - Gloria Sicilia-Argumedo
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico
| | - Leticia Riverón-Negrete
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico
| | - Alain de Jesús Hernández-Vázquez
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico
| | - Cristina Fernanadez-Mejia
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Avenida del Iman#1, 4th floor, Mexico City 04500, Mexico.
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Aguilera-Méndez A, Boone-Villa D, Nieto-Aguilar R, Villafaña-Rauda S, Molina AS, Sobrevilla JV. Role of vitamins in the metabolic syndrome and cardiovascular disease. Pflugers Arch 2021; 474:117-140. [PMID: 34518916 DOI: 10.1007/s00424-021-02619-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 08/14/2021] [Accepted: 08/30/2021] [Indexed: 12/25/2022]
Abstract
The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.
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Affiliation(s)
- Asdrubal Aguilera-Méndez
- Institute of Biological Chemistry Research, Universidad Michoacana de San Nicolás de Hidalgo, Av. J. Mújica, Edificio B3, Ciudad Universitaria, CP, 58030, Morelia, Michoacán, México.
| | - Daniel Boone-Villa
- School of Medicine, North Section, Universidad Autónoma de Coahuila, Piedras Negras, 26090, Coahuila, México
| | - Renato Nieto-Aguilar
- University Center for Postgraduate Studies and Research, School of Dentistry, Universidad Michoacana de San Nicolás de Hidalgo, 58337, Morelia, Michoacán, México
| | - Santiago Villafaña-Rauda
- Postgraduate Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, México
| | - Alfredo Saavedra Molina
- Institute of Biological Chemistry Research, Universidad Michoacana de San Nicolás de Hidalgo, Av. J. Mújica, Edificio B3, Ciudad Universitaria, CP, 58030, Morelia, Michoacán, México
| | - Janeth Ventura Sobrevilla
- School of Medicine, North Section, Universidad Autónoma de Coahuila, Piedras Negras, 26090, Coahuila, México
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18
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Bakir-Gungor B, Bulut O, Jabeer A, Nalbantoglu OU, Yousef M. Discovering Potential Taxonomic Biomarkers of Type 2 Diabetes From Human Gut Microbiota via Different Feature Selection Methods. Front Microbiol 2021; 12:628426. [PMID: 34512559 PMCID: PMC8424122 DOI: 10.3389/fmicb.2021.628426] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 05/03/2021] [Indexed: 12/24/2022] Open
Abstract
Human gut microbiota is a complex community of organisms including trillions of bacteria. While these microorganisms are considered as essential regulators of our immune system, some of them can cause several diseases. In recent years, next-generation sequencing technologies accelerated the discovery of human gut microbiota. In this respect, the use of machine learning techniques became popular to analyze disease-associated metagenomics datasets. Type 2 diabetes (T2D) is a chronic disease and affects millions of people around the world. Since the early diagnosis in T2D is important for effective treatment, there is an utmost need to develop a classification technique that can accelerate T2D diagnosis. In this study, using T2D-associated metagenomics data, we aim to develop a classification model to facilitate T2D diagnosis and to discover T2D-associated biomarkers. The sequencing data of T2D patients and healthy individuals were taken from a metagenome-wide association study and categorized into disease states. The sequencing reads were assigned to taxa, and the identified species are used to train and test our model. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization, Maximum Relevance and Minimum Redundancy, Correlation Based Feature Selection, and select K best approach. To test the performance of the classification based on the features that are selected by different methods, we used random forest classifier with 100-fold Monte Carlo cross-validation. In our experiments, we observed that 15 commonly selected features have a considerable effect in terms of minimizing the microbiota used for the diagnosis of T2D and thus reducing the time and cost. When we perform biological validation of these identified species, we found that some of them are known as related to T2D development mechanisms and we identified additional species as potential biomarkers. Additionally, we attempted to find the subgroups of T2D patients using k-means clustering. In summary, this study utilizes several supervised and unsupervised machine learning algorithms to increase the diagnostic accuracy of T2D, investigates potential biomarkers of T2D, and finds out which subset of microbiota is more informative than other taxa by applying state-of-the art feature selection methods.
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Affiliation(s)
- Burcu Bakir-Gungor
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - Osman Bulut
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - Amhar Jabeer
- Department of Computer Engineering, Faculty of Engineering, Abdullah Gül University, Kayseri, Turkey
| | - O. Ufuk Nalbantoglu
- Department of Computer Engineering, Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey
| | - Malik Yousef
- Department of Information Systems, Zefat Academic College, Zefat, Israel
- Galilee Digital Health Research Center, Zefat Academic College, Zefat, Israel
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19
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Biotinylated chitosan macromolecule based nanosystems: A review from chemical design to biological targets. Int J Biol Macromol 2021; 188:82-93. [PMID: 34363823 DOI: 10.1016/j.ijbiomac.2021.07.197] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 07/16/2021] [Accepted: 07/31/2021] [Indexed: 12/28/2022]
Abstract
World Health Organization estimates that 30-50% of cancers are preventable by healthy lifestyle choices, early detection and adequate therapy. When the conventional therapeutic strategies are still regulated by the lack of selectivity, multidrug resistance and severe toxic side effects, nanotechnology grants a new frontier for cancer management since it targets cancer cells and spares healthy tissues. This review highlights recent studies using biotin molecule combined with functional nanomaterials used in biomedical applications, with a particular attention on biotinylated chitosan-based nanosystems. Succinctly, this review focuses on five areas of recent advances in biotin engineering: (a) biotin features, (b) biotinylation approaches, (c) biotin functionalized chitosan based nanosystems for drug and gene delivery functions, (d) diagnostic and theranostic perspectives, and (e) author's inputs to the biotin-chitosan based tumour-targeting drug delivery structures. Precisely engineered biotinylated-chitosan macromolecules shaped into nanosystems are anticipated to emerge as next-generation platforms for treatment and molecular imaging modalities applications.
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20
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Syta E, Bobrowska-Korczak B. Nutrigenomics for the prevention and treatment diabetes. POSTEP HIG MED DOSW 2021. [DOI: 10.5604/01.3001.0014.7834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Diabetes mellitus is a metabolic disease that manifest itself hyperglycemia It is estimated
that about 422 million people worldwide are affected by this disease. Great hopes in the
prevention and support of pharmacological treatment of diabetes are associated with a new
scientific discipline, which is nutrigenomics. Lowering the reports in the field of physiology,
bromatology, genomics, proteomics, biochemistry or epigenetics, this field searches for and
explains the interactions of genes with food components at the molecular level. The article
presents the most important information on the bioactive effects of food (flavonoids, amino
acids, vitamins, fatty acids) on the expression of genes connected with secretion/action of
insulin and the metabolism of the glucose in the body. The article discusses the functions of
genes that work on the pathogenesis of diabetes development, and presents experimental
models in empirical research. In addition, it article presents the importance of epigenetic
factor in the development of type 2 diabetes mellitus, as well as basic informations in the
field of its diagnosis and differentiation.
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Affiliation(s)
- Ewa Syta
- Zakład Bromatologii, Wydział Farmaceutyczny, Warszawski Uniwersytet Medyczny
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21
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The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study. Cell Metab 2020; 32:379-390.e3. [PMID: 32652044 DOI: 10.1016/j.cmet.2020.06.011] [Citation(s) in RCA: 293] [Impact Index Per Article: 58.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 04/17/2020] [Accepted: 06/16/2020] [Indexed: 12/12/2022]
Abstract
The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.
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22
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Pastén-Hidalgo K, Riverón-Negrete L, Sicilia-Argumedo G, Canul-Medina G, Salazar-Anzures T, Tapia-Rodríguez M, Hernández-González EO, Roa-Espitia AL, Cedillo-Peláez C, Fernandez-Mejia C. Dietary Biotin Supplementation Impairs Testis Morphology and Sperm Quality. J Med Food 2020; 23:535-544. [PMID: 31660770 DOI: 10.1089/jmf.2019.0137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Supplements containing pharmacological concentrations of biotin are commercially available over the counter. Classical toxicity studies have considered biotin administration as harmless; however, recent investigations have shown that biotin supplementation modifies tissue morphology without changes in toxicity markers, raising concerns about the consequences of morphological changes on tissues' functions and the safety of pharmacological concentrations of the vitamin. Testes are very sensitive to toxicants, and testicular histology is a reliable method to study its function. In this work, we investigated the effects of dietary biotin supplementation on testis morphology and spermatogenesis function using an experimental model, in which we have not observed unfavorable effects on other tissue functions or toxicity markers. Male BALB/cAnNHsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 weeks. Compared to the control group, the biotin-supplemented mice presented remarkable testis morphology changes, including increased spermatogonia layers; the cellular mechanism involved is related to increased proliferation. Sperm count and serum testosterone levels were not affected, but spermatozoa motility and morphology were significantly impaired in the biotin-supplemented mice. These results caution against the use of supplements with high concentrations of biotin and indicate that biotin's pharmacological effects on morphology need to be considered in toxicological studies.
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Affiliation(s)
| | - Leticia Riverón-Negrete
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Gloria Sicilia-Argumedo
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Gustavo Canul-Medina
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Tonatiuh Salazar-Anzures
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Miguel Tapia-Rodríguez
- Unidad de Microscopía, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, Mexico
| | | | - Ana Lilia Roa-Espitia
- Departamento de Biología Celular, CINVESTAV-IPN, San Pedro Zacatenco, Mexico City, Mexico
| | - Carlos Cedillo-Peláez
- Departamento de Inmunología Experimental, Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Cristina Fernandez-Mejia
- Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Pediatría, Mexico City, Mexico
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23
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Bumrungpert A, Pavadhgul P, Chongsuwat R, Komindr S. Nutraceutical Improves Glycemic Control, Insulin Sensitivity, and Oxidative Stress in Hyperglycemic Subjects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20918687] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The aim of this research was to investigate the effects of nutraceuticals including bitter melon, fenugreek, cinnamon, alpha-lipoic acid, zinc, biotin, chromium, and cholecalciferol on glycemic control, insulin sensitivity, lipid profiles, oxidative stress, and inflammatory markers in hyperglycemia. The study design was a randomized, double-blind, placebo-controlled trial. Subjects with hyperglycemia were randomly divided into 2 groups. The treatment group ( n = 52) was given a nutraceutical and the control group ( n = 50) was provided with a placebo for 12 weeks. Fasting blood glucose (FBG), hemoglobin A1c (HbA1C), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profiles, biomarkers of oxidative stress, and inflammation were assessed before and after the intervention at 6 weeks and 12 weeks. Nutraceutical supplementation demonstrated a statistically significant decrease in FBG (13.4% and 18.9%), HbA1C (6.5% and 11.3%), and HOMA-IR (28.9% and 35.2%) compared with the placebo. Moreover, low-density lipoprotein-cholesterol (LDL-C) level was significantly reduced in the nutraceutical group (7.1% and 9.3%). Furthermore, the nutraceutical significantly decreased oxidative stress markers, oxidized LDL-C (14.8% and 18.9%) and malondialdehyde (16.6% and 26.2%) compared with the placebo. In conclusion, this nutraceutical can improve glycemic control, insulin resistance, lipid profiles, and oxidative stress markers in hyperglycemic subjects. Therefore, it has the potential to decrease cardiovascular disease risk factors. Clinical trial registration: TCTR20180907001, www.clinicaltrials.in.th.
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Affiliation(s)
- Akkarach Bumrungpert
- Research Center of Nutraceuticals and Natural Products for Health & Anti-Aging, College of Integrative Medicine, Dhurakij Pundit University, Bangkok, Thailand
| | - Patcharanee Pavadhgul
- Department of Nutrition, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - Rewadee Chongsuwat
- Department of Nutrition, Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - Surat Komindr
- Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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24
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Christ A, Lauterbach M, Latz E. Western Diet and the Immune System: An Inflammatory Connection. Immunity 2020; 51:794-811. [PMID: 31747581 DOI: 10.1016/j.immuni.2019.09.020] [Citation(s) in RCA: 506] [Impact Index Per Article: 101.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 07/24/2019] [Accepted: 09/24/2019] [Indexed: 02/06/2023]
Abstract
The consumption of Western-type calorically rich diets combined with chronic overnutrition and a sedentary lifestyle in Western societies evokes a state of chronic metabolic inflammation, termed metaflammation. Metaflammation contributes to the development of many prevalent non-communicable diseases (NCDs), and these lifestyle-associated pathologies represent a rising public health problem with global epidemic dimensions. A better understanding of how modern lifestyle and Western diet (WD) activate immune cells is essential for the development of efficient preventive and therapeutic strategies for common NCDs. Here, we review the current mechanistic understanding of how the Western lifestyle can induce metaflammation, and we discuss how this knowledge can be translated to protect the public from the health burden associated with their selected lifestyle.
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Affiliation(s)
- Anette Christ
- Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Infectious Diseases & Immunology, UMass Medical School, Worcester, MA 01605, USA
| | - Mario Lauterbach
- Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Bonn 53127, Germany
| | - Eicke Latz
- Institute of Innate Immunity, University Hospital Bonn, University of Bonn, Bonn 53127, Germany; Department of Infectious Diseases & Immunology, UMass Medical School, Worcester, MA 01605, USA; Center of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim 7491, Norway; German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany.
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25
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Thingholm LB, Rühlemann MC, Koch M, Fuqua B, Laucke G, Boehm R, Bang C, Franzosa EA, Hübenthal M, Rahnavard A, Frost F, Lloyd-Price J, Schirmer M, Lusis AJ, Vulpe CD, Lerch MM, Homuth G, Kacprowski T, Schmidt CO, Nöthlings U, Karlsen TH, Lieb W, Laudes M, Franke A, Huttenhower C. Obese Individuals with and without Type 2 Diabetes Show Different Gut Microbial Functional Capacity and Composition. Cell Host Microbe 2019; 26:252-264.e10. [PMID: 31399369 DOI: 10.1016/j.chom.2019.07.004] [Citation(s) in RCA: 297] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 05/17/2019] [Accepted: 07/16/2019] [Indexed: 02/07/2023]
Abstract
Obesity and type 2 diabetes (T2D) are metabolic disorders that are linked to microbiome alterations. However, their co-occurrence poses challenges in disentangling microbial features unique to each condition. We analyzed gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from German population and metabolic disease cohorts. Microbial taxonomic and functional profiles were analyzed along with medical histories, serum metabolomics, biometrics, and dietary data. Obesity was associated with alterations in microbiome composition, individual taxa, and functions with notable changes in Akkermansia, Faecalibacterium, Oscillibacter, and Alistipes, as well as in serum metabolites that correlated with gut microbial patterns. However, microbiome associations were modest for T2D, with nominal increases in Escherichia/Shigella. Medications, including antihypertensives and antidiabetics, along with dietary supplements including iron, were significantly associated with microbiome variation. These results differentiate microbial components of these interrelated metabolic diseases and identify dietary and medication exposures to consider in future studies.
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Affiliation(s)
- Louise B Thingholm
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
| | - Malte C Rühlemann
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
| | - Manja Koch
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Brie Fuqua
- Department of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Guido Laucke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
| | - Ruwen Boehm
- Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
| | - Eric A Franzosa
- Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
| | - Matthias Hübenthal
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany; Department of Dermatology, Venereology and Allergy, University Hospital, Schleswig-Holstein, 24105 Kiel, Germany
| | - Ali Rahnavard
- Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany
| | - Jason Lloyd-Price
- Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
| | - Melanie Schirmer
- Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
| | - Aldons J Lusis
- Department of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Chris D Vulpe
- College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
| | - Markus M Lerch
- Department of Medicine A, University Medicine Greifswald, 17475 Greifswald, Germany
| | - Georg Homuth
- Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany
| | - Tim Kacprowski
- Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; Research Group on Computational Systems Medicine, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Weihenstephan, Technical University of Munich, Freising-Weihenstephan 85354, Germany
| | - Carsten O Schmidt
- Institute for Community Medicine SHIP-KEF, University Medicine Greifswald, Greifswald 17475, Germany
| | - Ute Nöthlings
- Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany
| | - Tom H Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0315 Oslo, Norway
| | - Wolfgang Lieb
- Institute of Epidemiology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
| | - Matthias Laudes
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
| | - Curtis Huttenhower
- Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
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26
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Buzid A, Hayes PE, Glennon JD, Luong JH. Captavidin as a regenerable biorecognition element on boron-doped diamond for biotin sensing. Anal Chim Acta 2019; 1059:42-48. [DOI: 10.1016/j.aca.2019.01.058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 01/24/2019] [Accepted: 01/30/2019] [Indexed: 10/27/2022]
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DiNicolantonio JJ, McCarty M. Autophagy-induced degradation of Notch1, achieved through intermittent fasting, may promote beta cell neogenesis: implications for reversal of type 2 diabetes. Open Heart 2019; 6:e001028. [PMID: 31218007 PMCID: PMC6546199 DOI: 10.1136/openhrt-2019-001028] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/06/2019] [Indexed: 02/06/2023] Open
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28
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Moreno-Méndez E, Hernández-Vázquez A, Fernández-Mejía C. Effect of biotin supplementation on fatty acid metabolic pathways in 3T3-L1 adipocytes. Biofactors 2019; 45:259-270. [PMID: 30575140 DOI: 10.1002/biof.1480] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 10/19/2018] [Accepted: 11/13/2018] [Indexed: 12/30/2022]
Abstract
Several studies have shown that pharmacological concentrations of biotin decrease serum lipid concentrations and the expression of lipogenic genes. Previous studies on epididymal adipose tissue in mice revealed that 8 weeks of dietary biotin supplementation increased the protein abundance of the active form of AMPK and the inactive forms acetyl CoA carboxylase (ACC)-1 and - 2, and decreased serum free fatty acid concentrations but did not affect lipolysis. These data suggest that pharmacological concentrations of the vitamin might affect fatty acid metabolism. In this work, we investigated the effects of pharmacological biotin concentrations on fatty acid synthesis, oxidation, and uptake in 3T3-L1 adipocytes. Similar to observations in mice, biotin-supplemented 3T3-L1 adipose cells increased the protein abundance of active T172 -AMPK and inactive ACC-1 and -2 forms. No changes were observed in the expression of the transcriptional factor PPARα and carnitine-palmitoyltransferase-1 (CPT-1). Radiolabeled assays indicated a decrease in fatty acid synthesis; an increase in fatty acid oxidation and fatty acid incorporation rate into the lipid fraction between control cells and biotin-supplemented cells. The data revealed an increase in the mRNA abundance of the fatty acid transport proteins Fatp1 and Acsl1 but not Cd36 or Fatp4 mRNA. Furthermore, the abundance of glycerol phosphate acyl transferase-3 protein was increased. Triglyceride content was not affected. Lipid droplet numbers showed an increase and their areas were smaller in the biotin-supplemented group. In conclusion, these data indicate that biotin supplementation causes a decrease in fatty acid synthesis and an increase in its oxidation and uptake. © 2018 BioFactors, 45(2):259-270, 2019.
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Affiliation(s)
- Ericka Moreno-Méndez
- Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Instituto Nacional de Pediatria, Unidad de Genética de la Nutrición, Ciudad de México, Mexico
| | - Alain Hernández-Vázquez
- Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Instituto Nacional de Pediatria, Unidad de Genética de la Nutrición, Ciudad de México, Mexico
| | - Cristina Fernández-Mejía
- Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Instituto Nacional de Pediatria, Unidad de Genética de la Nutrición, Ciudad de México, Mexico
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29
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Kim M, Basharat A, Santosh R, Mehdi SF, Razvi Z, Yoo SK, Lowell B, Kumar A, Brima W, Danoff A, Dankner R, Bergman M, Pavlov VA, Yang H, Roth J. Reuniting overnutrition and undernutrition, macronutrients, and micronutrients. Diabetes Metab Res Rev 2019; 35:e3072. [PMID: 30171821 DOI: 10.1002/dmrr.3072] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/20/2018] [Accepted: 08/26/2018] [Indexed: 12/15/2022]
Abstract
Over-nutrition and its late consequences are a dominant theme in medicine today. In addition to the health hazards brought on by over-nutrition, the medical community has recently accumulated a roster of health benefits with obesity, grouped under "obesity paradox." Throughout the world and throughout history until the 20th century, under-nutrition was a dominant evolutionary force. Under-nutrition brings with it a mix of benefits and detriments that are opposite to and continuous with those of over-nutrition. This continuum yields J-shaped or U-shaped curves relating body mass index to mortality. The overweight have an elevated risk of dying in middle age of degenerative diseases while the underweight are at increased risk of premature death from infectious conditions. Micronutrient deficiencies, major concerns of nutritional science in the 20th century, are being neglected. This "hidden hunger" is now surprisingly prevalent in all weight groups, even among the overweight. Because micronutrient replacement is safe, inexpensive, and predictably effective, it is now an exceptionally attractive target for therapy across the spectrum of weight and age. Nutrition-related conditions worthy of special attention from caregivers include excess vitamin A, excess vitamin D, and deficiency of magnesium.
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Affiliation(s)
- Miji Kim
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Anam Basharat
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Ramchandani Santosh
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Syed F Mehdi
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Zanali Razvi
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Sun K Yoo
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Barbara Lowell
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Amrat Kumar
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Wunnie Brima
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
- Department of Medicine, Albert Einstein College of Medicine, New York, USA
| | - Ann Danoff
- Department of Medicine, Cpl. Michael J Crescenz Veterans Administration Medical Center, Philadelphia, PA, USA
| | - Rachel Dankner
- Department of Epidemiology and Preventive Medicine, School of Public Health, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Michael Bergman
- Department of Medicine, Division of Endocrinology, NYU School of Medicine, New York, NY, USA
| | - Valentin A Pavlov
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
- Center for Biomedical Science and Center for Bioelectric Medicine, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Huan Yang
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
- Center for Biomedical Science and Center for Bioelectric Medicine, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
| | - Jesse Roth
- Laboratory of Diabetes and Diabetes-Related Disorders, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
- Department of Medicine, Albert Einstein College of Medicine, New York, USA
- Center for Biomedical Science and Center for Bioelectric Medicine, The Feinstein Institute for Medical Research, Northwell Health, New York, USA
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Tixi-Verdugo W, Contreras-Ramos J, Sicilia-Argumedo G, German MS, Fernandez-Mejia C. Effects of Biotin Supplementation During the First Week Postweaning Increases Pancreatic Islet Area, Beta-Cell Proportion, Islets Number, and Beta-Cell Proliferation. J Med Food 2018; 21:274-281. [PMID: 29068758 PMCID: PMC5865616 DOI: 10.1089/jmf.2017.0077] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/14/2017] [Indexed: 02/07/2023] Open
Abstract
During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation. Biotin might have a potential action on islet maturation. Pharmacological concentrations of biotin have been found to modify islet morphology and function. In a previous study, we found that mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase in basal and glucose stimulated insulin secretion, enlarged islet size, and modified islet structure. In the present study, we investigated the effect of biotin on maturation features during the first week postweaning. Female BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 1 week after weaning. Compared with the control, biotin-supplemented mice showed an increase in pancreatic islet number and area in addition to an augmented proportion of beta-cells in the islet. These effects were related to an increase in beta-cell proliferation. No differences were found in insulin secretion, blood glucose concentrations, or serum insulin levels. These results indicate that biotin supplementation is capable of affecting beta-cell proliferation and might be a therapeutic agent for establishing strategies for regenerative medicine.
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Affiliation(s)
- Wilma Tixi-Verdugo
- Nutritional Genetics Unit, Biomedical Research Institute, National Autonomous University of Mexico/Pediatrics National Institute, Mexico City, Mexico
| | - Juan Contreras-Ramos
- Nutritional Genetics Unit, Biomedical Research Institute, National Autonomous University of Mexico/Pediatrics National Institute, Mexico City, Mexico
| | - Gloria Sicilia-Argumedo
- Nutritional Genetics Unit, Biomedical Research Institute, National Autonomous University of Mexico/Pediatrics National Institute, Mexico City, Mexico
| | - Michael S. German
- Diabetes Center/Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, USA
| | - Cristina Fernandez-Mejia
- Nutritional Genetics Unit, Biomedical Research Institute, National Autonomous University of Mexico/Pediatrics National Institute, Mexico City, Mexico
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Serhiyenko VA, Serhiyenko AA. Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment. World J Diabetes 2018; 9:1-24. [PMID: 29359025 PMCID: PMC5763036 DOI: 10.4239/wjd.v9.i1.1] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/09/2017] [Accepted: 12/29/2017] [Indexed: 02/06/2023] Open
Abstract
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of "silent" myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications. Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension, DLP, obesity, and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction. Methods of CAN assessment in clinical practice include assessment of symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term electrocardiography (ECG), QT interval prolongation, HR variability (24 h, classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex sensitivity, muscle sympathetic nerve activity, catecholamine assessment and cardiovascular sympathetic tests, heart sympathetic imaging. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced diet and physical activity; optimization of glycemic control; treatment of DLP; antioxidants, first of all α-lipoic acid (ALA), aldose reductase inhibitors, acetyl-L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; in severe cases-treatment of OH. The promising methods include prescription of prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), ALA, dihomo-γ-linolenic acid (DGLA), ω-3 polyunsaturated fatty acids (ω-3 PUFAs), and the simultaneous prescription of ALA, ω-3 PUFAs and DGLA, but the future investigations are needed. Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological, in the foreground midodrine and fludrocortisone acetate, treatment methods are necessary.
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Affiliation(s)
- Victoria A Serhiyenko
- Department of Endocrinology, Lviv National Medical University Named by Danylo Halitsky, Lviv 79010, Ukraine
| | - Alexandr A Serhiyenko
- Department of Endocrinology, Lviv National Medical University Named by Danylo Halitsky, Lviv 79010, Ukraine
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Neuroprotective potential of high-dose biotin. Med Hypotheses 2017; 109:145-149. [PMID: 29150274 DOI: 10.1016/j.mehy.2017.10.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 09/28/2017] [Accepted: 10/13/2017] [Indexed: 01/28/2023]
Abstract
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain-permeable phosphodiesterase-5 inhibitors.
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Lazo-de-la-Vega-Monroy ML, Larrieta E, Tixi-Verdugo W, Ramírez-Mondragón R, Hernández-Araiza I, German MS, Fernandez-Mejia C. Effects of dietary biotin supplementation on glucagon production, secretion, and action. Nutrition 2017; 43-44:47-53. [PMID: 28935144 DOI: 10.1016/j.nut.2017.06.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 05/27/2017] [Accepted: 06/04/2017] [Indexed: 01/09/2023]
Abstract
OBJECTIVE Despite increasing evidence that pharmacologic concentrations of biotin modify glucose metabolism, to our knowledge there have not been any studies addressing the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. The aim of this study was to investigate the effects of dietary biotin supplementation on glucagon expression, secretion, and action. METHODS Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 wk postweaning. Glucagon gene mRNA expression was measured by the real-time polymerase chain reaction. Glucagon secretion was assessed in isolated islets and by glucagon concentration in plasma. Glucagon action was evaluated by glucagon tolerance tests, phosphoenolpyruvate carboxykinase (Pck1) mRNA expression, and glycogen degradation. RESULTS Compared with the control group, glucagon mRNA and secretion were increased from the islets of the biotin-supplemented group. Fasting plasma glucagon levels were higher, but no differences between the groups were observed in nonfasting glucagon levels. Despite the elevated fasting glucagon levels, no differences were found in fasting blood glucose concentrations, fasting/fasting-refeeding glucagon tolerance tests, glycogen content and degradation, or mRNA expression of the hepatic gluconeogenic rate-limiting enzyme, Pck1. CONCLUSIONS These results demonstrated that dietary biotin supplementation increased glucagon expression and secretion without affecting fasting blood glucose concentrations or glucagon tolerance and provided new insights into the effect of biotin supplementation on glucagon production and action.
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Affiliation(s)
- Maria-Luisa Lazo-de-la-Vega-Monroy
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico; Division of Health Sciences, Department of Medical Sciences, University of Guanajuato, Guanajuato, Mexico
| | - Elena Larrieta
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico; Department of Gastroentrology, Salvador Zubirán National Institute of Health Sciences and Nutrition, Mexico City, Mexico
| | - Wilma Tixi-Verdugo
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Rafael Ramírez-Mondragón
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Ileana Hernández-Araiza
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico
| | - Michael S German
- Diabetes Center/Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California, USA
| | - Cristina Fernandez-Mejia
- Unit of Genetics of Nutrition, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Nacional de Pediatría, Mexico City, Mexico.
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Gene-Diet Interactions in Type 2 Diabetes: The Chicken and Egg Debate. Int J Mol Sci 2017; 18:ijms18061188. [PMID: 28574454 PMCID: PMC5486011 DOI: 10.3390/ijms18061188] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/23/2017] [Accepted: 05/26/2017] [Indexed: 02/07/2023] Open
Abstract
Consistent evidence from both experimental and human studies indicates that Type 2 diabetes mellitus (T2DM) is a complex disease resulting from the interaction of genetic, epigenetic, environmental, and lifestyle factors. Nutrients and dietary patterns are important environmental factors to consider in the prevention, development and treatment of this disease. Nutritional genomics focuses on the interaction between bioactive food components and the genome and includes studies of nutrigenetics, nutrigenomics and epigenetic modifications caused by nutrients. There is evidence supporting the existence of nutrient-gene and T2DM interactions coming from animal studies and family-based intervention studies. Moreover, many case-control, cohort, cross-sectional cohort studies and clinical trials have identified relationships between individual genetic load, diet and T2DM. Some of these studies were on a large scale. In addition, studies with animal models and human observational studies, in different countries over periods of time, support a causative relationship between adverse nutritional conditions during in utero development, persistent epigenetic changes and T2DM. This review provides comprehensive information on the current state of nutrient-gene interactions and their role in T2DM pathogenesis, the relationship between individual genetic load and diet, and the importance of epigenetic factors in influencing gene expression and defining the individual risk of T2DM.
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Samarasinghe S, Meah F, Singh V, Basit A, Emanuele N, Emanuele MA, Mazhari A, Holmes EW. BIOTIN INTERFERENCE WITH ROUTINE CLINICAL IMMUNOASSAYS: UNDERSTAND THE CAUSES AND MITIGATE THE RISKS. Endocr Pract 2017; 23:989-998. [PMID: 28534685 DOI: 10.4158/ep171761.ra] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The objectives of this report are to review the mechanisms of biotin interference with streptavidin/biotin-based immunoassays, identify automated immunoassay systems vulnerable to biotin interference, describe how to estimate and minimize the risk of biotin interference in vulnerable assays, and review the literature pertaining to biotin interference in endocrine function tests. METHODS The data in the manufacturer's "Instructions for Use" for each of the methods utilized by seven immunoassay system were evaluated. We also conducted a systematic search of PubMed/MEDLINE for articles containing terms associated with biotin interference. Available original reports and case series were reviewed. Abstracts from recent scientific meetings were also identified and reviewed. RESULTS The recent, marked, increase in the use of over-the-counter, high-dose biotin supplements has been accompanied by a steady increase in the number of reports of analytical interference by exogenous biotin in the immunoassays used to evaluate endocrine function. Since immunoassay methods of similar design are also used for the diagnosis and management of anemia, malignancies, autoimmune and infectious diseases, cardiac damage, etc., biotin-related analytical interference is a problem that touches every area of internal medicine. CONCLUSION It is important for healthcare personnel to become more aware of immunoassay methods that are vulnerable to biotin interference and to consider biotin supplements as potential sources of falsely increased or decreased test results, especially in cases where a lab result does not correlate with the clinical scenario. ABBREVIATIONS FDA = U.S. Food & Drug Administration FT3 = free tri-iodothyronine FT4 = free thyroxine IFUs = instructions for use LH = luteinizing hormone PTH = parathyroid hormone SA/B = streptavidin/biotin TFT = thyroid function test TSH = thyroid-stimulating hormone.
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McCarty MF. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin-Potential for Preventing or Slowing the Progression of Diabetic Complications. Healthcare (Basel) 2017; 5:E15. [PMID: 28335416 PMCID: PMC5371921 DOI: 10.3390/healthcare5010015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 02/23/2017] [Accepted: 03/06/2017] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS), and loss of nitric oxide (NO) bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Phycocyanobilin (PhyCB), the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4). Oxidation of BH4 yields dihydrobiopterin (BH2), which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA), typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to diabetic complications, high dose biotin has the potential to "pinch hit" for diminished NO by direct activation of soluble guanylate cyclase (sGC). High-dose biotin also may aid glycemic control via modulatory effects on enzyme induction in hepatocytes and pancreatic beta cells. Taurine, which suppresses diabetic complications in rodents, has the potential to reverse the inactivating impact of oxidative stress on sGC by boosting synthesis of hydrogen sulfide. Hence, it is proposed that concurrent administration of PhyCB, citrulline, taurine, and supranutritional doses of folate and biotin may have considerable potential for prevention and control of diabetic complications. Such a regimen could also be complemented with antioxidants such as lipoic acid, N-acetylcysteine, and melatonin-that boost cellular expression of antioxidant enzymes and glutathione-as well as astaxanthin, zinc, and glycine. The development of appropriate functional foods might make it feasible for patients to use complex nutraceutical regimens of the sort suggested here.
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Affiliation(s)
- Mark F McCarty
- Catalytic Longevity, 7831 Rush Rose Dr., Apt. 316, Carlsbad, CA 92009, USA.
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Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers. BIOMED RESEARCH INTERNATIONAL 2016; 2016:7276463. [PMID: 28105429 PMCID: PMC5220432 DOI: 10.1155/2016/7276463] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Revised: 11/28/2016] [Accepted: 11/30/2016] [Indexed: 11/18/2022]
Abstract
Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.
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He L, Hamm JA, Reddy A, Sams D, Peliciari-Garcia RA, McGinnis GR, Bailey SM, Chow CW, Rowe GC, Chatham JC, Young ME. Biotinylation: a novel posttranslational modification linking cell autonomous circadian clocks with metabolism. Am J Physiol Heart Circ Physiol 2016; 310:H1520-32. [PMID: 27084392 PMCID: PMC4935513 DOI: 10.1152/ajpheart.00959.2015] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 04/08/2016] [Indexed: 01/07/2023]
Abstract
Circadian clocks are critical modulators of metabolism. However, mechanistic links between cell autonomous clocks and metabolic processes remain largely unknown. Here, we report that expression of the biotin transporter slc5a6 gene is decreased in hearts of two distinct genetic mouse models of cardiomyocyte-specific circadian clock disruption [i.e., cardiomyocyte-specific CLOCK mutant (CCM) and cardiomyocyte-specific BMAL1 knockout (CBK) mice]. Biotinylation is an obligate posttranslational modification for five mammalian carboxylases: acetyl-CoA carboxylase α (ACCα), ACCβ, pyruvate carboxylase (PC), methylcrotonyl-CoA carboxylase (MCC), and propionyl-CoA carboxylase (PCC). We therefore hypothesized that the cardiomyocyte circadian clock impacts metabolism through biotinylation. Consistent with decreased slc5a6 expression, biotinylation of all carboxylases is significantly decreased (10-46%) in CCM and CBK hearts. In association with decreased biotinylated ACC, oleate oxidation rates are increased in both CCM and CBK hearts. Consistent with decreased biotinylated MCC, leucine oxidation rates are significantly decreased in both CCM and CBK hearts, whereas rates of protein synthesis are increased. Importantly, feeding CBK mice with a biotin-enriched diet for 6 wk normalized myocardial 1) ACC biotinylation and oleate oxidation rates; 2) PCC/MCC biotinylation (and partially restored leucine oxidation rates); and 3) net protein synthesis rates. Furthermore, data suggest that the RRAGD/mTOR/4E-BP1 signaling axis is chronically activated in CBK and CCM hearts. Finally we report that the hepatocyte circadian clock also regulates both slc5a6 expression and protein biotinylation in the liver. Collectively, these findings suggest that biotinylation is a novel mechanism by which cell autonomous circadian clocks influence metabolic pathways.
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Affiliation(s)
- Lan He
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - J Austin Hamm
- Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
| | - Alex Reddy
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - David Sams
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | | | - Graham R McGinnis
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Shannon M Bailey
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Chi-Wing Chow
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York
| | - Glenn C Rowe
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - John C Chatham
- Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama; and
| | - Martin E Young
- Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
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Rana S, Kumar S, Rathore N, Padwad Y, Bhushana S. Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases. Curr Genomics 2016; 17:261-78. [PMID: 27252592 PMCID: PMC4869012 DOI: 10.2174/1389202917666160202220422] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 06/18/2015] [Accepted: 06/22/2015] [Indexed: 02/07/2023] Open
Abstract
Post-human genome revelation observes the emergence of 'Nutigenomics' as one of the exciting scientific advancement influencing mankind around the world. Food or more precisely 'nutrition' has the major impact in defining the cause-response interaction between nutrient (diet) and human health. In addition to substantial understanding of nutrition-human-health interaction, bases of 'nutrigenomic' development foster on advent in transcriptomics, genomics, proteomics and metabolomics as well as insight into food as health supplement. Interaction of selected nutrient with associated genes in specific organ or tissue necessary to comprehend that how individual's genetic makeup (DNA transcribed into mRNA and then to proteins) respond to particular nutrient. It provided new opportunities to incorporate natural bioactive compounds into food for specific group of people with similar genotype. As inception of diabetes associated with change in gene expression of, not limited to, protein kinase B, insulin receptor, duodenal homeobox and glucokinase, thus, targeting such proteins by modifying or improving the nutritional availability or uptake may help to devise novel food, supplements, or nutraceuticals. In this article, various aspects of R&D in nutrigenomics are reviewed to ascertain its impact on human health, especially with life-style associated diseases.
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Affiliation(s)
- Shalika Rana
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Shiv Kumar
- Pharmacology and Toxicology Lab, Department of Food Nutraceuticals and Quality
Control, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Nikita Rathore
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
| | - Yogendra Padwad
- Pharmacology and Toxicology Lab, Department of Food Nutraceuticals and Quality
Control, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
| | - Shashi Bhushana
- Department of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur 176 061 (HP), India
- Academy of Scientific and Innovative Research, CSIR-Institute of Himalayan Bioresource Technology,
Palampur176 061 (HP), India
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Dakshinamurti K, Bagchi RA, Abrenica B, Czubryt MP. Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats. Can J Physiol Pharmacol 2015; 93:1103-10. [PMID: 26312779 DOI: 10.1139/cjpp-2014-0517] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Biotin is a B vitamin involved in multiple metabolic pathways. In humans, biotin deficiency is relatively rare but can cause dermatitis, alopecia, and perosis. Low biotin levels occur in individuals with type-2 diabetes, and supplementation with biotin plus chromium may improve blood sugar control. The acute effect on pancreatic gene expression of biotin repletion following chronic deficiency is unclear, therefore we induced biotin deficiency in adult male rats by feeding them a 20% raw egg white diet for 6 weeks. Animals were then randomized into 2 groups: one group received a single biotin supplement and returned to normal chow lacking egg white, while the second group remained on the depletion diet. After 1 week, pancreata were removed from biotin-deficient (BD) and biotin-repleted (BR) animals and RNA was isolated for microarray analysis. Biotin depletion altered gene expression in a manner indicative of inflammation, fibrosis, and defective pancreatic function. Conversely, biotin repletion activated numerous repair and anti-inflammatory pathways, reduced fibrotic gene expression, and induced multiple genes involved in pancreatic endocrine and exocrine function. A subset of the results was confirmed by quantitative real-time PCR analysis, as well as by treatment of pancreatic AR42J cells with biotin. The results indicate that biotin repletion, even after lengthy deficiency, results in the rapid induction of repair processes in the pancreas.
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Affiliation(s)
- Krishnamurti Dakshinamurti
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.,Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
| | - Rushita A Bagchi
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.,Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
| | - Bernard Abrenica
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.,Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
| | - Michael P Czubryt
- Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.,Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, 351 Tache Avenue, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
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Xiong F, Shen ZY, Li XK, Peng YN, Zhu HY, Zhang SP, Song YY, Du JL. An Improved Large-scale Preparation of Roche Lactone, an Intermediate for the Synthesis of (+)-Biotin. ORG PREP PROCED INT 2015. [DOI: 10.1080/00304948.2015.1025640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Dakshinamurti K. Vitamins and their derivatives in the prevention and treatment of metabolic syndrome diseases (diabetes),. Can J Physiol Pharmacol 2015; 93:355-62. [DOI: 10.1139/cjpp-2014-0479] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
A cluster of inter-related conditions such as central obesity, dyslipidemia, impaired glucose metabolism, and hypertension is referred to as Metabolic Syndrome, which is a risk factor for the development of type-2 diabetes. The micro- and macro-vascular complications of diabetes contribute to its morbidity and mortality. In addition to its calcitropic effect, vitamin D is a regulator of gene expression as well as cell proliferation and differentiation. Various cross-sectional and longitudinal cohort studies have indicated a beneficial effect from vitamin D supplementation on the development of type-2 diabetes. Binding of retinol-bound retinol-binding protein to a membrane-binding protein suppresses insulin signaling. All-trans retinoic acid, a derivative of vitamin A, reverses these effects, resulting in increased insulin sensitivity, suppression of the phosphoenolpyruvate carboxy kinase (PEPCK) gene, and the induction of the glucokinase gene. Glucokinase and PEPCK are also regulated in opposite directions by the vitamin biotin, acting at the transcriptional level. Biotin also regulates the synthesis of insulin by the islet of Langerhans cells of the pancreas. The increase in advanced glycation end products (AGEs) is implicated in the initiation and progression of diabetes-associated microvascular diseases. Benfotiamine, a derivative of thiamine, and pyridoxamine, a vitamer of vitamin B6, both have anti-AGE properties, making them valuable therapeutic adjuvants in the treatment of diabetic complications. Thus, various vitamins and their derivatives have profound therapeutic potential in the prevention and treatment of type-2 diabetes.
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Affiliation(s)
- Krishnamurti Dakshinamurti
- St. Boniface Hospital Research Centre, Faculty of Medicine, University of Manitoba, 351 Tache Avenue Winnipeg, MB R2H 2A6, Canada
- St. Boniface Hospital Research Centre, Faculty of Medicine, University of Manitoba, 351 Tache Avenue Winnipeg, MB R2H 2A6, Canada
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Abstract
Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.
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Affiliation(s)
- Toshinobu Kuroishi
- Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.,Division of Oral Immunology, Department of Oral Biology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
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Berná G, Oliveras-López MJ, Jurado-Ruíz E, Tejedo J, Bedoya F, Soria B, Martín F. Nutrigenetics and nutrigenomics insights into diabetes etiopathogenesis. Nutrients 2014; 6:5338-69. [PMID: 25421534 PMCID: PMC4245593 DOI: 10.3390/nu6115338] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 10/17/2014] [Accepted: 11/04/2014] [Indexed: 01/17/2023] Open
Abstract
Diabetes mellitus (DM) is considered a global pandemic, and the incidence of DM continues to grow worldwide. Nutrients and dietary patterns are central issues in the prevention, development and treatment of this disease. The pathogenesis of DM is not completely understood, but nutrient-gene interactions at different levels, genetic predisposition and dietary factors appear to be involved. Nutritional genomics studies generally focus on dietary patterns according to genetic variations, the role of gene-nutrient interactions, gene-diet-phenotype interactions and epigenetic modifications caused by nutrients; these studies will facilitate an understanding of the early molecular events that occur in DM and will contribute to the identification of better biomarkers and diagnostics tools. In particular, this approach will help to develop tailored diets that maximize the use of nutrients and other functional ingredients present in food, which will aid in the prevention and delay of DM and its complications. This review discusses the current state of nutrigenetics, nutrigenomics and epigenomics research on DM. Here, we provide an overview of the role of gene variants and nutrient interactions, the importance of nutrients and dietary patterns on gene expression, how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients and the dietary interventions that may help to prevent the onset of DM.
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Affiliation(s)
- Genoveva Berná
- Department of Stem Cells, Andalusian Center of Molecular Biology and Regenerative Medicine, University Pablo Olavide (CABIMER-UPO), Seville 41091, Spain.
| | - María Jesús Oliveras-López
- Department of Stem Cells, Andalusian Center of Molecular Biology and Regenerative Medicine, University Pablo Olavide (CABIMER-UPO), Seville 41091, Spain.
| | - Enrique Jurado-Ruíz
- Department of Stem Cells, Andalusian Center of Molecular Biology and Regenerative Medicine, University Pablo Olavide (CABIMER-UPO), Seville 41091, Spain.
| | - Juan Tejedo
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), CIBER of Diabetes and Associated Metabolic Diseases, Instituto de Salud Carlos III, Madrid 28029, Spain.
| | - Francisco Bedoya
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), CIBER of Diabetes and Associated Metabolic Diseases, Instituto de Salud Carlos III, Madrid 28029, Spain.
| | - Bernat Soria
- Department of Stem Cells, Andalusian Center of Molecular Biology and Regenerative Medicine, University Pablo Olavide (CABIMER-UPO), Seville 41091, Spain.
| | - Franz Martín
- Department of Stem Cells, Andalusian Center of Molecular Biology and Regenerative Medicine, University Pablo Olavide (CABIMER-UPO), Seville 41091, Spain.
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Ghosal A, Sekar TV, Said HM. Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process. Am J Physiol Gastrointest Liver Physiol 2014; 307:G365-73. [PMID: 24904078 PMCID: PMC4121639 DOI: 10.1152/ajpgi.00157.2014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na(+)-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na(+)-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS.
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Affiliation(s)
- Abhisek Ghosal
- Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California
| | - Thillai V. Sekar
- Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California
| | - Hamid M. Said
- Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California
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