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Yu H, Guo B, Miao Z, Chen C, Song Y, Yang J. A high-fat diet suppresses growth hormone synthesis and secretion by influencing the Vit D receptor and Pit1. Endocrine 2025:10.1007/s12020-025-04270-3. [PMID: 40369297 DOI: 10.1007/s12020-025-04270-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 04/30/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND A long-term high-fat diet (HFD) leads to excessive lipid deposition, which may cause many diseases, including NAFLD, diabetes, and thyroid dysfunction. In addition, HFD leads to a decrease in serum growth hormone (GH) levels to further increase lipid deposition and obesity. However, the mechanism of such reduction of GH has not been fully elucidated. METHODS Male Sprague-Dawley rats were fed a regular diet (CD) or a high-fat diet (HFD) for 29 weeks. GH synthesis and secretion were evaluated in pituitary and blood samples, respectively. An in vitro model was constructed by treating cultured cells with palmitic acid (PA). Vit D receptor (VDR) plasmids (OE-VDR), paricalcitol and VDR knockdown virus (sh-VDR) were used to overexpress or depress the activation of VDR during PA treatment of GH3 cells. The GH content, lipid content, and relevant expression of different molecules were measured in pituitary and cell samples. RESULTS A HFD decreased the levels of circulating GH and the expression of Gh in the anterior pituitary gland tissues of rats. In vitro, PA treatment decreased Pit1 and Gh expression in cultured GH3 cells. VDR expression was reduced in the rat pituitary tissues under HFD conditions and in PA-treated GH3 cells. The overexpression and knockdown of VDR increased and decreased the expression of Pit1 and Gh, respectively. Paricalcitol antagonized the decrease in the expression of Pit1 and Gh caused by PA treatment. CONCLUSIONS HFD induced lipid deposition in the pituitary may cause GH deficiency, and VDR - Pit1 may be at least partially involved in the process.
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Affiliation(s)
- Huimin Yu
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
| | - Boning Guo
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
- Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Zhiwei Miao
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Key Laboratery of Endocine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Jinan, China
| | - Chen Chen
- Endocrinology, SBMS, Faculty of Medicine, The University of Queensland, St Lucia, Qld, Australia
| | - Yongfeng Song
- Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
| | - Jianmei Yang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
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González-Casanova JE, Navarro-Marquez M, Saez-Tamayo T, Angarita L, Durán-Agüero S, Fuentes-Barría H, Bermúdez V, Rojas-Gómez DM. New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis. Int J Mol Sci 2025; 26:3690. [PMID: 40332335 PMCID: PMC12027591 DOI: 10.3390/ijms26083690] [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: 12/24/2024] [Revised: 03/28/2025] [Accepted: 03/28/2025] [Indexed: 05/08/2025] Open
Abstract
Metformin, a widely used antidiabetic drug, modulates the cellular physiology and metabolism of various body tissues, including adipose tissue. Adipogenesis, a complex process in which mesenchymal stem cells (MSC) differentiate into functional adipocytes, plays a key role in metabolic health and represents a potential therapeutic target for diverse metabolic disorders. Notably, recent evidence suggests that metformin modulates adipocyte differentiation. This narrative review explores the effects of metformin on cellular metabolism, with a particular focus on adipogenesis. The findings compiled in this review show that metformin regulates glucose and lipid metabolism in multiple tissues, including skeletal muscle, adipose tissue, liver, and intestine. Furthermore, metformin modulates adipogenesis through AMP-activated protein kinase (AMPK)-dependent and independent mechanisms in 3T3-L1 cells and adipose-derived stem cells. The review also emphasizes that metformin can promote or inhibit adipogenesis and lipid accumulation, depending on its concentration. Additionally, metformin attenuates inflammatory pathways by reducing the production of proinflammatory cytokines such as IL-6, MCP-1, and COX-2. Finally, evidence supports that vitamin D enhances the anti-inflammatory actions of metformin and promotes cell differentiation toward a beige adipocyte phenotype. In summary, this review examines the molecular actions of metformin to propose potential new therapeutic strategies for managing obesity and related metabolic diseases.
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Affiliation(s)
| | - Mario Navarro-Marquez
- Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago 8370321, Chile; (M.N.-M.); (T.S.-T.)
| | - Tamara Saez-Tamayo
- Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago 8370321, Chile; (M.N.-M.); (T.S.-T.)
| | - Lissé Angarita
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Concepción 4260000, Chile;
| | - Samuel Durán-Agüero
- Escuela de Nutrición y Dietética, Facultad de Ciencias de la Rehabilitación y Calidad de Vida, Universidad San Sebastián, Sede Los Leones, Lota 2465, Providencia, Santiago 7500000, Chile;
| | - Héctor Fuentes-Barría
- Vicerrectoría de Investigación e Innovación, Universidad Arturo Prat, Iquique 1100000, Chile;
| | - Valmore Bermúdez
- Facultad de Ciencias de la Salud, Centro de Investigaciones en Ciencias de la vida, Universidad Simón Bolívar, Barranquilla 080022, Colombia
| | - Diana Marcela Rojas-Gómez
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Santiago 8370321, Chile
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Imerbsin N, Shantavasinkul PC, Witoonpanich P, Sirivarasai J, Taonam N, Phanachet P, Warodomwichit D, Jayanama K, Boonyawat K, Somlaw N, Ongphiphadhanakul B, Nakawiro D, Tangwongchai S. Vitamin D and Cognitive Impairment. Nutrients 2025; 17:1301. [PMID: 40284166 PMCID: PMC12030256 DOI: 10.3390/nu17081301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 03/31/2025] [Accepted: 04/01/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Vitamin D deficiency is recognized as a significant public health concern, and it has been identified as one of the potentially modifiable risk factors for mild cognitive impairment (MCI). However, evidence regarding the relationship between vitamin D status and cognitive function remains conflicting. OBJECTIVE Therefore, this study aimed to examine the prevalence of vitamin D deficiency in the Thai elderly population and an association between vitamin D status and cognitive function, adiposity, and insulin sensitivity. METHODS This study enrolled participants aged 55-80 years with normal cognitive function (normal group) or MCI from the prospective cohort in the "Holistic approach of Alzheimer's disease in Thai people (HADThai study)". We used the baseline clinical data to determine the prevalence of vitamin D deficiency and its association between vitamin D status and cognitive function, adiposity, and insulin sensitivity. RESULTS A total of 718 subjects (71.9% women) with a mean age of 65.7 ± 5.8 years and a mean BMI of 23.9 ± 3.7 kg/m2 were enrolled. There were 470 (65.5%) participants with normal cognitive function and 248 (34.5%) with MCI. Vitamin D status did not differ significantly between individuals with normal cognitive function and those with MCI. The prevalence of vitamin D deficiency (<20 ng/mL) and vitamin D inadequacy (<30 ng/mL) in both normal cognitive function and MCI was around 6.5% and 40.0%, respectively. While serum 25(OH)D concentrations were inversely associated with body mass index (BMI), body fat, %body fat, and the homeostasis model assessment of insulin resistance (HOMA-IR), no relationship was found between vitamin D status and cognitive function. CONCLUSIONS Our study emphasized the high prevalence of vitamin D inadequacy among elderly individuals and an inverse association of vitamin D status and adiposity and insulin resistance. These findings emphasize the importance of addressing vitamin D deficiency in the elderly population to improve overall health outcomes. Nevertheless, our results do not support a direct role of vitamin D status in cognitive decline in this population. Further research, particularly studies with longer follow-up periods and the inclusion of patients with dementia with details of vitamin D supplementation, is needed to clarify the potential role of vitamin D in cognitive decline and neurodegenerative diseases.
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Affiliation(s)
- Nalinee Imerbsin
- Doctor of Philosophy Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University, Bangkok 10400, Thailand;
- Department of Pharmacy, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Prapimporn Chattranukulchai Shantavasinkul
- Division of Nutrition and Biochemical Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.T.); (P.P.); (D.W.)
- Nutrition Unit, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Pirada Witoonpanich
- Division of Neurology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Jintana Sirivarasai
- Nutrition Unit, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Naphat Taonam
- Division of Nutrition and Biochemical Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.T.); (P.P.); (D.W.)
| | - Pariya Phanachet
- Division of Nutrition and Biochemical Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.T.); (P.P.); (D.W.)
| | - Daruneewan Warodomwichit
- Division of Nutrition and Biochemical Medicine, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand; (N.T.); (P.P.); (D.W.)
| | - Kulapong Jayanama
- Department of Medicine, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10400, Thailand;
| | - Kochawan Boonyawat
- Division of Hematology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Nicha Somlaw
- Division of Clinical Nutrition, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Boonsong Ongphiphadhanakul
- Division of Endocrinology and Metabolism, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Daochompu Nakawiro
- Department of Psychiatry, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Sookjaroen Tangwongchai
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
- Center of Excellence in Cognitive Impairment and Dementia, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Lee MJ. Vitamin D Enhancement of Adipose Biology: Implications on Obesity-Associated Cardiometabolic Diseases. Nutrients 2025; 17:586. [PMID: 39940444 PMCID: PMC11820181 DOI: 10.3390/nu17030586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/27/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
Vitamin D is activated into 1α,25(OH)2D through two hydroxylation steps that are primarily catalyzed by 25-hydroxylase in the liver and 1α-hydroxylase in the kidneys. The active form of vitamin D regulates myriads of cellular functions through its nuclear receptor, vitamin D receptor (VDR). Vitamin D metabolizing enzymes and VDR are expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including the recruitment and differentiation of adipose stem cells into adipocytes and metabolic, endocrine, and immune properties. Obesity is associated with low vitamin D status, which is thought to be explained by its sequestration in large mass of adipose tissues as well as dysregulated vitamin D metabolism. Low vitamin D status in obesity may negatively impact adipose biology leading to adipose tissue dysfunctions, the major pathological factors for cardiometabolic diseases in obesity. In this review, the current understanding of vitamin D metabolism and its molecular mechanisms of actions, focusing on vitamin D-VDR regulation of adipose biology with their implications on obesity-associated diseases, is discussed. Whether improving vitamin D status leads to reductions in adiposity and risks for cardiometabolic diseases is also discussed.
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Affiliation(s)
- Mi-Jeong Lee
- Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, HI 96822, USA
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Talandashti MK, Shahinfar H, Delgarm P, Jazayeri S. Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials. Neurol Sci 2025; 46:651-670. [PMID: 39404918 DOI: 10.1007/s10072-024-07794-0] [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: 06/02/2024] [Accepted: 10/03/2024] [Indexed: 01/28/2025]
Abstract
BACKGROUND The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results. METHODS We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool. RESULTS Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes. CONCLUSION The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial.
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Affiliation(s)
| | - Hossein Shahinfar
- Department of Nutrition, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
- Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Pedram Delgarm
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Shima Jazayeri
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
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Payet T, Astier J, Bournot L, Sicard F, Robert S, Lacroix R, Wabitsch M, Landrier J, Mounien L. Vitamin D modulates the content of inflammatory microRNAs in extracellular vesicles from human adipocyte cells in inflammatory context. Biofactors 2025; 51:e70003. [PMID: 39887543 PMCID: PMC11779547 DOI: 10.1002/biof.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/17/2025] [Indexed: 02/01/2025]
Abstract
Inflammation of adipose tissue is a contributing factor to many chronic diseases associated with obesity. We previously showed that micronutrients such as vitamin D (VD) limited this metabolic inflammation by decreasing inflammatory markers expression including miR-155 (microRNA-155) or miR-146a in different in vitro and in vivo models. These miRNAs could be incorporated into extracellular vesicles (EVs) in order to modulate the activity of target cells. Nevertheless, the role of VD on the miRNAs contained in EVs from adipose tissue in inflammatory conditions remains unclear. In this study, we used a human model of SGBS (Simpson-Golabi-Behmel syndrome) adipocytes preincubated with 1,25(OH)2D (the active form of VD) before an inflammatory stress with tumor necrosis factor α (TNFα). First, we confirmed by quantitative PCR that the expression of classical inflammatory factors (TNFα and chemokine ligand 2 [CCL2/MCP1]), miR-146a, and miR-155 was increased significantly under inflammatory conditions in SGBS cells and that VD prevented this up-regulation. Secondly, transmission electron microscope imaging of EVs preparations in supernatant allowed visualization of small and large vesicles under these conditions. Then, EVs were obtained with isolation kit and the expression of miR-155 and miR-146a were measured. The expression of miR-155 under TNFα effect was increased in EVs while miR-146a was not detected. Moreover, we also showed that the TNFα-mediated expression of miR-155 in EVs was significantly reduced by a VD pre-incubation of cells. Using miRNA PCR array, we also identified 33 miRNAs, organized in 5 clusters that were differentially regulated by TNFα and VD. Bioinformatic analysis of biological pathways revealed that the different miRNAs targeting genes that are involved in important cell process such as the regulation of transcription or protein phosphorylation. In conclusion, these results support for the first time that VD modulated the expression of miRNAs in EVs from adipocytes, which could represent a new mechanism of regulation of inflammation by micronutrients.
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Affiliation(s)
- Thomas Payet
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
| | - Julien Astier
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
| | - Lorrine Bournot
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
- Biomeostasis CRONutritional Behavior and Metabolic DisordersLa Penne‐sur‐HuveauneFrance
| | - Flavie Sicard
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
- PhenoMARS Aix‐Marseille Technology PlatformCriBiomMarseilleFrance
| | - Stéphane Robert
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
| | - Romaric Lacroix
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
- Department of HaematologyBiogenopole, CHU La Timone, AP‐HMMarseilleFrance
| | - Martin Wabitsch
- Department of Pediatrics and Adolescent MedicineUlm University Medical CenterUlmGermany
| | - Jean‐François Landrier
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
- PhenoMARS Aix‐Marseille Technology PlatformCriBiomMarseilleFrance
| | - Lourdes Mounien
- Aix Marseille University, INSERM, INRAE, C2VNMarseilleFrance
- PhenoMARS Aix‐Marseille Technology PlatformCriBiomMarseilleFrance
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Radivojevic N, Grujicic SS, Suljagic V, Stojkovic S, Arsovic K, Jakovljevic S, Bukurov B, Arsovic N. Prognostic value of serum 25-hydroxyvitamin D levels and malnutrition status on postoperative complications in patients following laryngectomy with neck dissection. Eur Arch Otorhinolaryngol 2025; 282:341-349. [PMID: 39438295 DOI: 10.1007/s00405-024-09046-5] [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: 06/22/2024] [Accepted: 10/14/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Postoperative complications (PCs) following total laryngectomy remain a significant challenge, with recent investigations directed toward the impact of nutrition status and vitamin D deficiency. OBJECTIVES To elucidate the association between preoperative vitamin D level status, malnutrition risk score, and surgical and survival outcomes in patients with advanced laryngeal cancer following total laryngectomy. STUDY DESIGN Prospective cohort study. METHODS Sixty-four patients with advanced laryngeal carcinoma treated with total laryngectomy were included in the study. Serum levels of 25(OH) D3 were measured employing a commercial chemiluminescent immunoassay kit, while nutrition status was evaluated using the nutrition risk index (NRI) and Malnutrition universal screening tool (MUST). RESULTS The mean serum 25(OH) D level was 37.1 ± 19.4 nmol/L (range 11.0-100.6 nmol/L), with 47% of patients exhibiting vitamin D deficiency and 31% displaying insufficiency. Medium/high MUST score had 53% of patients, and moderate/severe NRI was verified in 48% of patients. Univariate logistic regression analysis identified MUST score, GPS score, neutrophil-to-lymphocyte ratio, and circulating 25(OH) D levels as predictive for the occurrence of PCs. In multivariate analysis, MUST score and circulating 25(OH) D levels remained significantly associated with PCs. Patients with high nutrition risk had significantly lower two-year OS rates compared to the medium and low nutrition risk groups, respectively (30% vs. 62% and 83%, p = 0.010). CONCLUSION Early identification of malnourished or patients with vitamin D deficiency and those who would benefit from specific nutritional support could be beneficial for minimizing the risk of development of surgical complications and help improve our clinical outcomes.
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Affiliation(s)
- Nemanja Radivojevic
- Faculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, Belgrade, 11000, Serbia.
| | | | - Vesna Suljagic
- Medical Faculty, Military Medical Academy, Department of Healthcare-Related Infection Control, University of Defense, Military Medical Academy, Belgrade, Serbia
| | - Stefan Stojkovic
- Clinic of Gastroenterology and Hepatology, University Clinical Center of Serbia, Belgrade, Serbia
| | - Konstantin Arsovic
- Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Belgrade, Serbia
| | - Sasa Jakovljevic
- Faculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, Belgrade, 11000, Serbia
| | - Bojana Bukurov
- Faculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, Belgrade, 11000, Serbia
| | - Nenad Arsovic
- Faculty of Medicine, University of Belgrade, Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center of Serbia, Pasterova 2, Belgrade, 11000, Serbia
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Malicka A, Ali A, MacCannell ADV, Roberts LD. Brown and beige adipose tissue-derived metabokine and lipokine inter-organ signalling in health and disease. Exp Physiol 2024. [PMID: 39591977 DOI: 10.1113/ep092008] [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: 07/19/2024] [Accepted: 10/24/2024] [Indexed: 11/28/2024]
Abstract
Adipose tissue has an established endocrine function through the secretion of adipokines. However, a role for bioactive metabolites and lipids, termed metabokines and lipokines, is emerging in adipose tissue-mediated autocrine, paracrine and endocrine signalling and inter-organ communication. Traditionally seen as passive entities, metabolites are now recognized for their active roles in regulating cellular signalling and local and systemic metabolism. Distinct from white adipose tissue, specific endocrine functions have been attributed to thermogenic brown and beige adipose tissues. Brown and beige adipose tissues have been identified as sources of metabokines and lipokines, which influence diverse metabolic pathways, such as fatty acid β-oxidation, mitochondrial function and glucose homeostasis, across a range of tissues, including skeletal muscle, adipose tissue and heart. This review explores the intricate signalling mechanisms of brown and beige adipose tissue-derived metabokines and lipokines, emphasizing their roles in maintaining metabolic homeostasis and their potential dysregulation in metabolic diseases. Furthermore, we discuss the therapeutic potential of targeting these pathways, proposing that precise modulation of metabokine receptors and transporters could offer superior specificity and efficacy in comparison to conventional approaches, such as β-adrenergic signalling-stimulated activation of brown adipose tissue thermogenesis. Understanding the complex interactions between adipokines, metabokines and lipokines is essential for developing a systems-level approach to new interventions for metabolic disorders, underscoring the need for continued research in this rapidly evolving field.
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Affiliation(s)
- Anna Malicka
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK
| | - Aysha Ali
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK
| | - Amanda D V MacCannell
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK
| | - Lee D Roberts
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK
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Park CY, Shin S, Han SN. Multifaceted Roles of Vitamin D for Diabetes: From Immunomodulatory Functions to Metabolic Regulations. Nutrients 2024; 16:3185. [PMID: 39339785 PMCID: PMC11435169 DOI: 10.3390/nu16183185] [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: 08/30/2024] [Revised: 09/15/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Numerous studies have established associations between vitamin D and diabetes. The vitamin D receptor is widely distributed throughout the human body, including in pancreatic beta cells (β-cells), hepatocytes, and immune cells. Therefore, vitamin D's effect on the risk, progression, or complications of diabetes may be mediated through various mechanisms. These include the regulation of insulin secretion or sensitivity and modulation of β-cell function and its immunomodulatory and anti-inflammatory effects. This review extensively explores the relationship between vitamin D status and diabetes, as well as the preventive or therapeutic effects of vitamin D supplementation on diabetes from human studies. Additionally, it examines in detail the impact of vitamin D on immune and inflammatory responses in the diabetic milieux and β-cell function to better understand the underlying mechanisms through which vitamin D influences diabetes.
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Affiliation(s)
- Chan Yoon Park
- Department of Food & Nutrition, College of Life Care Science Technology, The University of Suwon, Hwaseong-si 18323, Republic of Korea
| | - Sunhye Shin
- Department of Food and Nutrition, College of Science and Convergence Technology, Seoul Women's University, Seoul 01797, Republic of Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
- Research Institute of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
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10
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Bournot L, Payet T, Sicard F, Breniere T, Astier J, Roux J, Bariohay B, Landrier JF. Aging alone or combined with obesity increases white adipose tissue inflammatory status in male mice. Sci Rep 2024; 14:16268. [PMID: 39009694 PMCID: PMC11251036 DOI: 10.1038/s41598-024-67179-3] [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: 01/23/2024] [Accepted: 07/09/2024] [Indexed: 07/17/2024] Open
Abstract
White adipose tissue (WAT) has been recognized as a fundamental and crucial organ of interest in research focusing on inflammation during obesity or aging. WAT is also proposed as a significant component of cholecalciferol and 25-hydroxyvitamin D (25(OH)D) storage, which participates in the decrease of 25(OH)D plasma levels reported during aging and obesity. In the present study, we evaluated WAT and plasma cholecalciferol and 25(OH)D content together with inflammatory status to highlight the putative relationship between vitamin D status and inflammatory process during aging alone or combined with obesity. Circulating cholecalciferol and 25(OH)D and the stored quantity of cholecalciferol and 25(OH)D in WAT were quantified in young and old mice fed a control or obesogenic diet. The inflammation was assessed by measuring plasma inflammatory cytokines, mRNA, and microRNAs inflammatory-associated in WAT. The combination of aging and obesity decreased 25(OH)D plasma levels but did not modify circulating inflammatory markers. A cumulative effect of aging and obesity was observed in WAT, with rising mRNA inflammatory cytokines, notably Ccl5 and Tnf. Interestingly, aging and obesity-associated were also characterized by increased inflammatory microRNA expression. The inflammatory parameters in WAT were negatively correlated with the plasma 25(OH)D but positively correlated with the quantity of cholecalciferol and 25(OH)D in WAT. These results support the cumulative effect of obesity and aging in aggravation of WAT inflammation and suggest that accumulation of cholecalciferol and 25(OH)D in WAT could constitute a mechanism to counteract WAT inflammation during aging and obesity.
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Affiliation(s)
- Lorrine Bournot
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France
- Biomeostasis, 13070, La Penne Sur Huveaune, France
| | - Thomas Payet
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France
| | - Flavie Sicard
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France
- PhenoMARS, CriBiom, Marseille, France
| | - Thomas Breniere
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France
| | - Julien Astier
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France
| | - Julien Roux
- Biomeostasis, 13070, La Penne Sur Huveaune, France
| | | | - Jean-François Landrier
- Aix-Marseille Université, C2VN, INRAE, INSERM, 13000, Marseille, France.
- PhenoMARS, CriBiom, Marseille, France.
- C2VN, UMR 1260 INRAE/1263 INSERM/Aix Marseille Université, 27 Bd Jean Moulin, 13385, Marseille Cedex 05, France.
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11
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Ramalingam L, Mabry B, Menikdiwela KR, Moussa H, Moustaid-Moussa N. Enhanced Metabolic Effects of Fish Oil When Combined with Vitamin D in Diet-Induced Obese Male Mice. Biomolecules 2024; 14:474. [PMID: 38672490 PMCID: PMC11048485 DOI: 10.3390/biom14040474] [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: 03/01/2024] [Revised: 03/30/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Vitamin D (vit D) and fish oil (FO) both offer unique health benefits, however, their combined effects have not been evaluated in obesity and nonalcoholic fatty liver disease (NAFLD). Hence, we hypothesized that vit D and FO supplementation would have additive effects in reducing obesity-associated inflammation and NAFLD. Male C57BL6 mice were split into four groups and fed a high fat (HF) diet supplemented with a low (HF; +200 IU vit D) or high dose of vitamin D (HF + D; +1000 IU vit D); combination of vit D and FO (HF-FO; +1000 IU vit D); or only FO (HF-FO; +200 IU vit D) for 12 weeks. We measured body weight, food intake, glucose tolerance, and harvested epididymal fat pad and liver for gene expression analyses. Adiposity was reduced in groups supplemented with both FO and vit D. Glucose clearance was higher in FO-supplemented groups compared to mice fed HF. In adipose tissue, markers of fatty acid synthesis and oxidation were comparable in groups that received vit D and FO individually in comparison to HF. However, the vit D and FO group had significantly lower fatty acid synthesis and higher oxidation compared to the other groups. Vit D and FO also significantly improved fatty acid oxidation, despite similar fatty acid synthesis among the four groups in liver. Even though we did not find additive effects of vit D and FO, our data provide evidence that FO reduces markers of obesity in the presence of adequate levels of vit D.
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Affiliation(s)
- Latha Ramalingam
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Brennan Mabry
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
| | - Kalhara R. Menikdiwela
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Hanna Moussa
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
- Department of Physics & Astronomy, College of Arts & Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA
| | - Naima Moustaid-Moussa
- Nutrigenomics, Inflammation and Obesity Research Laboratory, Department of Nutritional Sciences, Texas Tech University (TTU), Lubbock, TX 79409, USA (K.R.M.)
- Obesity Research Institute, Office of Research & Innovation, Texas Tech University (TTU), Lubbock, TX 79409, USA
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12
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Park CY, Han SN. Vitamin D and obesity. ADVANCES IN FOOD AND NUTRITION RESEARCH 2024; 109:221-247. [PMID: 38777414 DOI: 10.1016/bs.afnr.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
An inverse association between vitamin D status and obesity has been reported across diverse populations and age groups in humans. In animal model of diet-induced obesity, dysregulation of vitamin D metabolism has been observed. However, the causal relationship between vitamin D status and obesity is not conclusive. Several explanations, such as volumetric dilution, sequestration of vitamin D into adipose tissue, and limited sunlight exposure, have been suggested as the underlying mechanisms linking poor vitamin D status and obesity. Vitamin D can modulate adipose tissue biology, spanning from adipocyte differentiation to adipocyte apoptosis and energy metabolism, indicating its potential impact on adiposity. In this chapter, we will review the prevalence of vitamin D deficiency and determinants of vitamin D deficiency among different populations, as well as changes in vitamin D metabolism associated with obesity. Additionally, we will review vitamin D's regulation of adipogenesis and lipogenesis at the cellular level in order to gain a deeper understanding of the underlying mechanisms linking vitamin D levels and obesity.
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Affiliation(s)
- Chan Yoon Park
- Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong-si, Gyeonggi-do, Republic of Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Republic of Korea; Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Republic of Korea.
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13
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Wi D, Park CY. 1,25-dihydroxyvitamin D 3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes. Nutr Res Pract 2024; 18:1-18. [PMID: 38352211 PMCID: PMC10861344 DOI: 10.4162/nrp.2024.18.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/01/2023] [Accepted: 12/06/2023] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND/OBJECTIVES Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alleviates ER stress in adipocytes. MATERIALS/METHODS 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS Treatment with 1,25(OH)2D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2D3 treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)2D3 administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2D3 inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS Our data suggest that 1,25(OH)2D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.
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Affiliation(s)
- Dain Wi
- Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong 18323, Korea
| | - Chan Yoon Park
- Department of Food & Nutrition, College of Health Science, The University of Suwon, Hwaseong 18323, Korea
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14
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Kwon DH, Hwang J, You H, Kim NY, Lee GY, Han SN. Effects of an in vitro vitamin D treatment on the inflammatory responses in visceral adipose tissue from Ldlr-/- mice. Nutr Res Pract 2024; 18:19-32. [PMID: 38352213 PMCID: PMC10861343 DOI: 10.4162/nrp.2024.18.1.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/26/2023] [Accepted: 11/16/2023] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND/OBJECTIVES Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlrtm1Her/J (Ldlr-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)2D3 for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)2D3 treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)2D3 treatment. The 1,25(OH)2D3 treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.
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Affiliation(s)
- Deok Hoon Kwon
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Jungwon Hwang
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Hyeyoung You
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Na Young Kim
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Ga Young Lee
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Korea
- Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul 08826, Korea
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15
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Prado Y, Aravena D, Gatica S, Llancalahuen FM, Aravena C, Gutiérrez-Vera C, Carreño LJ, Cabello-Verrugio C, Simon F. From genes to systems: The role of food supplementation in the regulation of sepsis-induced inflammation. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166909. [PMID: 37805092 DOI: 10.1016/j.bbadis.2023.166909] [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: 03/24/2023] [Revised: 09/29/2023] [Accepted: 09/29/2023] [Indexed: 10/09/2023]
Abstract
Systemic inflammation includes a widespread immune response to a harmful stimulus that results in extensive systemic damage. One common example of systemic inflammation is sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Under the pro-inflammatory environment of sepsis, oxidative stress contributes to tissue damage due to dysfunctional microcirculation that progressively causes the failure of multiple organs that ultimately triggers death. To address the underlying inflammatory condition in critically ill patients, progress has been made to assess the beneficial effects of dietary supplements, which include polyphenols, amino acids, fatty acids, vitamins, and minerals that are recognized for their immuno-modulating, anticoagulating, and analgesic properties. Therefore, we aimed to review and discuss the contribution of food-derived supplementation in the regulation of inflammation from gene expression to physiological responses and summarize the precedented potential of current therapeutic approaches during systemic inflammation.
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Affiliation(s)
- Yolanda Prado
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Diego Aravena
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Sebastian Gatica
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Felipe M Llancalahuen
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Cristobal Aravena
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
| | - Cristián Gutiérrez-Vera
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile
| | - Leandro J Carreño
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile
| | - Claudio Cabello-Verrugio
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Laboratory of Muscle Pathology, Fragility and Aging, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Chile
| | - Felipe Simon
- Laboratory of Integrative Physiopathology, Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Millennium Nucleus of Ion Channel-Associated Diseases, Santiago, Chile.
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16
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Popa AD, Niță O, Caba L, Gherasim A, Graur M, Mihalache L, Arhire LI. From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation. Metabolites 2023; 14:4. [PMID: 38276294 PMCID: PMC10820276 DOI: 10.3390/metabo14010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/12/2023] [Accepted: 12/18/2023] [Indexed: 01/27/2024] Open
Abstract
Obesity affects more than one billion people worldwide and often leads to cardiometabolic chronic comorbidities. It induces senescence-related alterations in adipose tissue, and senescence is closely linked to obesity. Fully elucidating the pathways through which vitamin D exerts anti-inflammatory effects may improve our understanding of local adipose tissue inflammation and the pathogenesis of metabolic disorders. In this narrative review, we compiled and analyzed the literature from diverse academic sources, focusing on recent developments to provide a comprehensive overview of the effect of vitamin D on inflammation associated with obesity and senescence. The article reveals that the activation of the NF-κB (nuclear factor kappa B subunit 1) and NLRP3 inflammasome (nucleotide-binding domain, leucine-rich-containing, pyrin domain-containing-3) pathways through the toll-like receptors, which increases oxidative stress and cytokine release, is a common mechanism underlying inflammation associated with obesity and senescence, and it discusses the potential beneficial effect of vitamin D in alleviating the development of subclinical inflammation. Investigating the main target cells and pathways of vitamin D action in adipose tissue could help uncover complex mechanisms of obesity and cellular senescence. This review summarizes significant findings related to opportunities for improving metabolic health.
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Affiliation(s)
- Alina Delia Popa
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
| | - Otilia Niță
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
| | - Lavinia Caba
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
| | - Andreea Gherasim
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
| | - Mariana Graur
- Faculty of Medicine and Biological Sciences, University “Ștefan cel Mare” of Suceava, 720229 Suceava, Romania;
| | - Laura Mihalache
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
| | - Lidia Iuliana Arhire
- Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania; (A.D.P.); (A.G.); (L.M.); (L.I.A.)
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Karkeni E, Payet T, Astier J, Sicard F, Mounien L, Landrier JF. Proposal of a bioinformatics approach to predict molecular mechanisms involved in inflammatory response: case of ATRA and 1,25(OH) 2D in adipocytes. Epigenetics 2023; 18:2201516. [PMID: 37071788 PMCID: PMC10116923 DOI: 10.1080/15592294.2023.2201516] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023] Open
Abstract
Several inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)2D) as previously shown. In the present study, we aimed to implement a new bioinformatics approach to unveil commonly regulated signalling pathways through a combination of gene and miRNA expression sets impacted by ATRA and 1,25(OH)2D in adipocytes. In a first set of experiments, we focused only our attention on ATRA and demonstrated that it reduced LPS-mediated miRNA expression (miR-146a, miR-150, and miR-155) in mouse adipose tissue, in adipocyte cultures, and in adipocyte-derived vesicles. This result was confirmed in TNFα-induced miRNA in human adipocytes. Then, bioinformatic analysis highlighted that both ATRA and 1,25(OH)2D-regulated genes and miRNA converge to the canonical 'nuclear factor Kappa B (NF-κB) signalling pathway.' Altogether, these results showed that ATRA has anti-inflammatory effects on miRNA expression. In addition, the proposed bioinformatic model converges to NF-κB signalling pathway that has been previously demonstrated to be regulated by ATRA and 1,25(OH)2D, thus confirming the interest of such approach.
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Affiliation(s)
- Esma Karkeni
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Thomas Payet
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Julien Astier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Flavie Sicard
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
- PhenoMars, C2VN, INRAE, INSERM, CriBiom, Marseille, France
| | - Lourdes Mounien
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
- PhenoMars, C2VN, INRAE, INSERM, CriBiom, Marseille, France
| | - Jean-François Landrier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
- PhenoMars, C2VN, INRAE, INSERM, CriBiom, Marseille, France
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18
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Lu S, Cao ZB. Interplay between Vitamin D and Adipose Tissue: Implications for Adipogenesis and Adipose Tissue Function. Nutrients 2023; 15:4832. [PMID: 38004226 PMCID: PMC10675652 DOI: 10.3390/nu15224832] [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: 10/19/2023] [Revised: 11/10/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
Adipose tissue encompasses various types, including White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and beige adipose tissue, each having distinct roles in energy storage and thermogenesis. Vitamin D (VD), a fat-soluble vitamin, maintains a complex interplay with adipose tissue, exerting significant effects through its receptor (VDR) on the normal development and functioning of adipocytes. The VDR and associated metabolic enzymes are widely expressed in the adipocytes of both rodents and humans, and they partake in the regulation of fat metabolism and functionality through various pathways. These encompass adipocyte differentiation, adipogenesis, inflammatory responses, and adipokine synthesis and secretion. This review primarily appraises the role and mechanisms of VD in different adipocyte differentiation, lipid formation, and inflammatory responses, concentrating on the pivotal role of the VD/VDR pathway in adipogenesis. This insight furnishes new perspectives for the development of micronutrient-related intervention strategies in the prevention and treatment of obesity.
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Affiliation(s)
| | - Zhen-Bo Cao
- School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China;
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19
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Payet T, Valmori M, Astier J, Svilar L, Sicard F, Tardivel C, Ghossoub R, Martin JC, Landrier JF, Mounien L. Vitamin D Modulates Lipid Composition of Adipocyte-Derived Extracellular Vesicles Under Inflammatory Conditions. Mol Nutr Food Res 2023; 67:e2300374. [PMID: 37712099 DOI: 10.1002/mnfr.202300374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 07/31/2023] [Indexed: 09/16/2023]
Abstract
SCOPE Adipocyte-derived extracellular vesicles (AdEVs) convey lipids that can play a role in the energy homeostasis. Vitamin D (VD) has been shown to limit the metabolic inflammation as it decreases inflammatory markers expression in adipose tissue (AT). However, VD effect on adipocytes-derived EVs has never been investigated. METHODS AND RESULTS Thus, the aim of this study is to evaluate the AdEVs lipid composition by LC-MS/MS approach in 3T3-L1 cells treated with VD or/and pro-inflammatory factor (tumor necrosis factor α [TNFα]). Among all lipid species, four are highlighted (glycerolipids, phospholipids, lysophospholipids, and sphingolipids) with a differential content between small (sEVs) and large EVs (lEVs). This study also observes that VD alone modulates EV lipid species involved in membrane fluidity and in the budding of membrane. EVs treated with VD under inflammatory conditions have different lipid profiles than the control group, which is more pronounced in lEVs. Indeed, 25 lipid species are significantly modulated in lEVs, compared with only seven lipid species in sEVs. CONCLUSIONS This study concludes that VD, alone or under inflammatory conditions, is associated with specific lipidomic signature of sEVs and lEVs. These observations reinforce current knowledge on the anti-inflammatory effect of VD.
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Affiliation(s)
- Thomas Payet
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
| | - Marie Valmori
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- BIOMET, Marseille, France
| | - Julien Astier
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
| | - Ljubica Svilar
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- BIOMET, Marseille, France
| | - Flavie Sicard
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- BIOMET, Marseille, France
- PhenoMARS Aix-Marseille Technology Platform, Marseille, France
| | | | - Rania Ghossoub
- Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe Labellisée Ligue 2018, CNRS, Inserm, Institut Paoli Calmettes, Aix-Marseille Université, Marseille, France
| | - Jean-Charles Martin
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- BIOMET, Marseille, France
| | - Jean-François Landrier
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- PhenoMARS Aix-Marseille Technology Platform, Marseille, France
| | - Lourdes Mounien
- Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, France
- PhenoMARS Aix-Marseille Technology Platform, Marseille, France
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Almaghrbi H, Al-Shafai M, Al-Asmakh M, Bawadi H. Association of Vitamin D Genetic Risk Score with Noncommunicable Diseases: A Systematic Review. Nutrients 2023; 15:4040. [PMID: 37764823 PMCID: PMC10537716 DOI: 10.3390/nu15184040] [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: 08/18/2023] [Revised: 09/09/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Background and Aims: The genetic risk score (GRS) is an important tool for estimating the total genetic contribution or susceptibility to a certain outcome of interest in an individual, taking into account their genetic risk alleles. This study aims to systematically review the association between the GRS of low vitamin D with different noncommunicable diseases/markers. Methods: The article was first registered in PROSPERO CRD42023406929. PubMed and Embase were searched from the time of inception until March 2023 to capture all the literature related to the vitamin D genetic risk score (vD-GRS) in association with noncommunicable diseases. This was performed using comprehensive search terms including "Genetic Risk Score" OR "Genetics risk assessment" OR "Genome-wide risk score" AND "Vitamin D" OR 25(HO)D OR "25-hydroxyvitamin D". Results: Eleven eligible studies were included in this study. Three studies reported a significant association between vD-GRS and metabolic parameters, including body fat percentage, body mass index, glycated hemoglobin, and fasting blood glucose. Moreover, colorectal cancer overall mortality and the risk of developing arterial fibrillation were also found to be associated with genetically deprived vitamin D levels. Conclusions: This systematic review highlights the genetic contribution of low-vitamin-D-risk single nucleotides polymorphisms (SNPs) as an accumulative factor associated with different non-communicable diseases/markers, including cancer mortality and the risk of developing obesity, type 2 diabetes, and cardiovascular diseases such as arterial fibrillation.
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Affiliation(s)
- Heba Almaghrbi
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (H.A.); (M.A.-S.); (M.A.-A.)
| | - Mashael Al-Shafai
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (H.A.); (M.A.-S.); (M.A.-A.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Maha Al-Asmakh
- Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (H.A.); (M.A.-S.); (M.A.-A.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Hiba Bawadi
- Department of Human Nutrition, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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21
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Lee JH, Kim YA, Kim YS, Lee Y, Seo JH. Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study. Nutrients 2023; 15:3043. [PMID: 37447368 DOI: 10.3390/nu15133043] [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: 06/13/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
Vitamin D deficiency (VDD) is increasingly prevalent on a global scale and is connected to chronic health issues including diabetes, obesity, and inflammation. This study aimed to investigate the association between VDD and various clinical parameters including glycated hemoglobin (HbA1c), body mass index (BMI), and inflammatory markers. This cross-sectional cohort study included Korean men and women aged 50 years and older (290 men, 125 women); VDD was classified as serum 25-hydroxyvitamin D (25[OH]D) levels below 20 ng/mL. Vitamin D deficiency was more prevalent in men (64.5%) compared to that in women (35.2%). Men with VDD had higher fat mass and HbA1c levels, lower muscle strength, and worse physical performance. Among women, VDD was associated with higher BMI, HbA1c, tumor necrosis factor-alpha (TNF-α), and creatinine levels. In women, 25(OH)D levels exhibited an inverse relationship with HbA1c, BMI, and TNF-α concentrations. However, there were no differences in the levels of interleukin-6 and interleukin-1 beta according to vitamin D status in both men and women. Vitamin D deficiency is linked to higher HbA1c, BMI, and inflammatory markers in older Korean women, thus warranting the maintenance of sufficient vitamin D levels for overall health.
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Affiliation(s)
- Ji Hyun Lee
- Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Ye An Kim
- Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Young Sik Kim
- Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Young Lee
- Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
| | - Je Hyun Seo
- Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
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22
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Liu J, Song Y, Wang Y, Hong H. Vitamin D/vitamin D receptor pathway in non-alcoholic fatty liver disease. Expert Opin Ther Targets 2023; 27:1145-1157. [PMID: 37861098 DOI: 10.1080/14728222.2023.2274099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 10/18/2023] [Indexed: 10/21/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, but underlying mechanisms are not fully understood. In recent years, a growing body of evidence has emphasized the therapeutic role of vitamin D in NAFLD, but the specific mechanism remains to be investigated. AREAS COVERED This review summarized the roles of vitamin D/VDR (vitamin D receptor) pathway in different types of liver cells (such as hepatocytes, hepatic stellate cells, liver macrophages, T lymphocytes, and other hepatic immune cells) in case of NAFLD. Meanwhile, the effects of pathways in the gut-liver axis, adipose tissue-liver axis, and skeletal muscle-liver axis on the development of NAFLD were further reviewed. Relevant literature was searched on PubMed for the writing of this review. EXPERT OPINION The precise regulation of regional vitamin D/VDR signaling pathway based on cell-specific or tissue-specific function will help clarify the potential mechanism of vitamin D in NAFLD, which may provide new therapeutic targets to improve the safety and efficacy of vitamin D based drugs.
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Affiliation(s)
- Jingqi Liu
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Yang Song
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Ye Wang
- Xiamen Institute of Geriatric Rehabilitation, Department of Geriatrics, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian, China
| | - Huashan Hong
- Fujian Key Laboratory of Vascular Aging, Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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23
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Wu J, Atkins A, Downes M, Wei Z. Vitamin D in Diabetes: Uncovering the Sunshine Hormone's Role in Glucose Metabolism and Beyond. Nutrients 2023; 15:nu15081997. [PMID: 37111216 PMCID: PMC10142687 DOI: 10.3390/nu15081997] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/18/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Over the last decades, epidemiology and functional studies have started to reveal a pivotal role of vitamin D in both type 1 and type 2 diabetes pathogenesis. Acting through the vitamin D receptor (VDR), vitamin D regulates insulin secretion in pancreatic islets and insulin sensitivity in multiple peripheral metabolic organs. In vitro studies and both T1D and T2D animal models showed that vitamin D can improve glucose homeostasis by enhancing insulin secretion, reducing inflammation, reducing autoimmunity, preserving beta cell mass, and sensitizing insulin action. Conversely, vitamin D deficiency has been shown relevant in increasing T1D and T2D incidence. While clinical trials testing the hypothesis that vitamin D improves glycemia in T2D have shown conflicting results, subgroup and meta-analyses support the idea that raising serum vitamin D levels may reduce the progression from prediabetes to T2D. In this review, we summarize current knowledge on the molecular mechanisms of vitamin D in insulin secretion, insulin sensitivity, and immunity, as well as the observational and interventional human studies investigating the use of vitamin D as a treatment for diabetes.
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Affiliation(s)
- Jie Wu
- Department of Physiology and Biomedical Engineering, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
| | - Annette Atkins
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Michael Downes
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Zong Wei
- Department of Physiology and Biomedical Engineering, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
- Division of Endocrinology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
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24
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Konuksever D, Yücel Karakaya SP, Bölük O, Koçak M, Kılıç BO, Saç RÜ. The association of vitamin D deficiency with hemogram-derived inflammatory biomarkers in children. Nutr Metab Cardiovasc Dis 2022; 32:2418-2423. [PMID: 35973886 DOI: 10.1016/j.numecd.2022.07.012] [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] [Received: 03/29/2022] [Revised: 07/12/2022] [Accepted: 07/17/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS One of the extraosseous effects of vitamin D is that it is a potent modulator of inflammatory processes. Many studies have demonstrated the inverse association between vitamin D and inflammation. Therefore, we hypothesize that vitamin D deficiency may affect the inflammatory markers derived from hemogram parameters [neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), platelet distribution width (PDW), red blood cell distribution width (RDW)] in healthy children. METHODS AND RESULTS We conducted a retrospective study on healthy children. From 2015 to 2020, 16,321 children with simultaneous vitamin D and hemogram measurements were identified from electronic records. Participants were divided into 2 groups according to whether they had vitamin D deficiency or not. The relationship between vitamin D status and the levels of inflammatory markers was analyzed. All inflammatory markers showed statistically significant differences between vitamin D status (p < 0.001 for all). Vitamin D levels were significantly negatively correlated with NLR (r = -0.285), PLR (r = -0.257), PDW (r = -0.181), and positively correlated with LMR (r = 0.218), and RDW (r = 0.057). In logistic regression analysis, age (OR = 1.15, 95% CI: 1.14-1.16), gender (OR = 1.66, 95% CI: 1.54-1.78), LMR (OR = 0.96, 95% CI: 0.95-0.98), PLR (OR = 1.003, 95% CI: 1.001-1.004), and RDW (OR = 1.10, 95%CI: 1.07-1.13) were found to be independent predictors for vitamin D deficiency. CONCLUSIONS Statistically significant differences were detected between vitamin D status and inflammatory parameters. However, the difference between the median values of vitamin D groups was very small and the degree of correlation was very weak. Therefore, the clinical significance of the difference should be questioned.
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Affiliation(s)
- Dilek Konuksever
- Pediatrics, Turkish Ministry of Health Ankara City Hospital, Bilkent, Ankara, Turkey.
| | | | - Oğuz Bölük
- Pediatrics, Ankara Training and Research Hospital, Ankara, Turkey
| | - Mesut Koçak
- Pediatrics, Turkish Ministry of Health Ankara City Hospital, Bilkent, Ankara, Turkey
| | | | - Rukiye Ünsal Saç
- Pediatrics, Ankara Training and Research Hospital, Ankara, Turkey
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25
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Effects of Vitamin D Supplementation on Adipose Tissue Inflammation and NF-κB/AMPK Activation in Obese Mice Fed a High-Fat Diet. Int J Mol Sci 2022; 23:ijms231810915. [PMID: 36142842 PMCID: PMC9506068 DOI: 10.3390/ijms231810915] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 11/20/2022] Open
Abstract
Adipose tissue expansion is strongly associated with increased adipose macrophage infiltration and adipocyte-derived pro-inflammatory cytokines, contributing to obesity-associated low-grade inflammation. Individuals with vitamin D deficiency have an increased prevalence of obesity and increased circulating inflammatory cytokines. However, the effect of vitamin D supplementation on obesity-induced inflammation remains controversial. Male C57BL/6J mice received a low-fat (10% fat) or high-fat (HF, 60% fat diet) containing 1000 IU vitamin D/kg diet, or HF supplemented with 10,000 IU vitamin D/kg diet for 16 weeks (n = 9/group). Vitamin D supplementation did not decrease HF-increased body weight but attenuated obesity-induced adipose hypertrophy and macrophage recruitment as demonstrated by the number of crown-like structures. Vitamin D supplementation significantly reduced the mRNA expression of CD11c, CD68, and iNOS, specific for inflammatory M1-like macrophages, and decreased serum levels of NO. In addition, significant reductions in pro-inflammatory gene expression of IL-6, MCP-1, and TNFα and mRNA levels of ASC-1, CASP1, and IL-1β involved in NLRP3 inflammasome were found in obese mice supplemented with vitamin D. Vitamin D supplementation significantly increased obesity-decreased AMPK activity and suppressed HF-increased NF-κB phosphorylation in adipose tissue from obese mice. These observed beneficial effects of vitamin D supplementation on adipose tissue expansion, macrophage recruitment, and inflammation might be related to AMPK/NF-κB signaling.
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26
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Bennour I, Haroun N, Sicard F, Mounien L, Landrier JF. Recent insights into vitamin D, adipocyte, and adipose tissue biology. Obes Rev 2022; 23:e13453. [PMID: 35365943 DOI: 10.1111/obr.13453] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 03/18/2022] [Indexed: 02/06/2023]
Abstract
Several studies bring strong evidence for an active role of vitamin D and its metabolites in physiological adipocyte and adipose tissue processes in adulthood. This role includes effects of vitamin D on key adipose tissue and adipocyte biology parameters, including adipogenesis, energy metabolism, and inflammation. Interestingly, recent data also point to a role of maternal vitamin D deficiency in adipocyte and adipose tissue metabolic programming in offspring. This review summarizes the current state of knowledge on the biological effect of vitamin D on adipocyte/adipose tissue physiology.
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Affiliation(s)
- Imene Bennour
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Nicole Haroun
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Flavie Sicard
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,PhenoMARS Aix-Marseille Technology Platform, CriBiom, Marseille, France
| | - Lourdes Mounien
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,PhenoMARS Aix-Marseille Technology Platform, CriBiom, Marseille, France
| | - Jean-François Landrier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,PhenoMARS Aix-Marseille Technology Platform, CriBiom, Marseille, France
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27
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Vitamin D and Visceral Obesity in Humans: What Should Clinicians Know? Nutrients 2022; 14:nu14153075. [PMID: 35893929 PMCID: PMC9332747 DOI: 10.3390/nu14153075] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/18/2022] [Accepted: 07/22/2022] [Indexed: 02/06/2023] Open
Abstract
The extraskeletal effect of vitamin D on adipose tissue biology and modulation in human obesity is of great interest and has been extensively investigated. Current evidence from preclinical and clinical studies in human adipose tissue suggests that the anti-inflammatory effects of vitamin D are evident and consistent, whereas the effects of vitamin D on adipocyte differentiation, adipogenesis, and energy metabolism and the effects of vitamin D supplementation on adipokine levels are inconclusive. Interventional studies related to medical and surgical weight loss in humans have shown small or no improvement in vitamin D status. Additionally, the benefit of vitamin D supplementation for the reduction in visceral adipose tissue has only been demonstrated in a few studies. Overall, the findings on the relationship between vitamin D and visceral adipose tissue in humans are still inconclusive. Further studies are required to confirm the beneficial effects of vitamin D on ameliorating adipose tissue dysfunction.
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28
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Maternal Vitamin D Deficiency in Mice Increases White Adipose Tissue Inflammation in Offspring. Cells 2022; 11:cells11132024. [PMID: 35805107 PMCID: PMC9265671 DOI: 10.3390/cells11132024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/20/2022] [Accepted: 06/23/2022] [Indexed: 12/15/2022] Open
Abstract
Vitamin D is acknowledged to play an important biological and metabolic role in adipose tissue, which is also the main storage site for this vitamin. Its anti-inflammatory effect in adipocytes and adipose tissue has notably been highlighted in adult mice. This vitamin is also crucial during fetal development since maternal vitamin D deficiency is suspected to program future metabolic disorders. Based on these observations, the aim of this study was to evaluate the consequences of maternal vitamin D deficiency (VDD) on white adipose tissue inflammation in adult offspring fed with normal or obesogenic diet (high-fat diet). White adipose tissue morphology, RNA and miRNA expression profiles, and signaling pathways were studied in adult males and females. In males, a HF diet coupled with maternal VDD increased expression of RNA and miRNA linked to inflammation leading to over-representation of inflammatory pathways. Interestingly, genomic and epigenetic profiles were associated with activation of the NF-kB signaling pathway and adiposity index. In females, no major modulation of inflammatory pathways was observed under VDD, contrarily to males. We concluded that maternal VDD coupled with HF diet activated inflammatory pathway in adipose tissue of the offspring, in a sex-dependent manner. Such activation is strongly related to activation of NF-kB signaling and increased adiposity only in males.
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29
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Oral vitamin D 3 supplementation for femtosecond LASIK-associated dry eye vitamin D for LASIK dry eye syndrome. Int Ophthalmol 2022; 42:3145-3152. [PMID: 35551580 DOI: 10.1007/s10792-022-02314-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 04/18/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE To assess the effect of oral vitamin D3 supplementation in dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). SETTING Liuzhou Worker's Hospital. DESIGN This prospective study included 90 patients selected between January and December in 2019, who underwent FS-LASIK operation in our hospital and had obvious symptoms indicating dry eyes 1 month after operation. The subjects were randomly divided into two groups: The experimental group (n = 45) received vitamin D3 2000 IU/D continuously for 12 weeks; the control group (n = 45) did not take vitamin D3 orally. Ocular surface disease index (OSDI), Tear breakup time (TBUT) and Schirmer's test I were evaluated premedication and 1,3,6 months after treatment. Serum vitamin D3 level and the mean concentration of cytokine IL-6, IL-17, IL-23 in t ears were also measured. RESULTS One month after treatment, the mean OSDI score of the experimental group (11.67 ± 8.53) was significantly lower than that of the control group (23.82 ± 13.22) (P = 0.007). TBUT (10.71 ± 1.02 s) and Schirmer I (9.36 ± 0.40 mm) of the experimental group were higher than those of the control group (7.49 ± 1.29 s and 7.51 ± 0.44 mm). The OSDI (10.25 ± 5.49) was significantly lower than those of the control group(20.22 ± 6.23) and TBUT (10.75 ± 1.09 s) and Schirmer I test value (11.34 ± 0.39 mm) of the experimental group were significantly higher than those of the control group (8.36 ± 1.23, 8.12 ± 0.50) at 3 months after treatment. There were significant differences in OSDI, TBUT (P < 0.05) and Schirmer I test value between the two groups at 6 months after treatment. Serum vitamin D3 level was negatively correlated with OSDI score (r = - 0.90; P = 0.00) and positively correlated with Schirmer I test (r = 0.88; P = 0.00), TBUT score (r = 0.89; P = 0.00) and TMH (r = 0.80; P = 0.00). IL-17 level was shown to be significantly correlated with TBUT(r = - 0.25, P = 0.014) and Schirmer I test (r = - 0.21, P = 0.018). IL-6 level was significantly correlated with OSDI (R = 0.18, P = 0.020) and TBUT (R = 0.20, P = 0.019).
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30
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Thams L, Stounbjerg NG, Hvid LG, Mølgaard C, Hansen M, Damsgaard CT. Effects of high dairy protein intake and vitamin D supplementation on body composition and cardiometabolic markers in 6-8-y-old children-the D-pro trial. Am J Clin Nutr 2022; 115:1080-1091. [PMID: 35015806 DOI: 10.1093/ajcn/nqab424] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/23/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Increasing evidence suggests that prevention of lifestyle diseases should begin early. Dairy protein and vitamin D can affect body composition and cardiometabolic markers, yet evidence among well-nourished children is sparse. OBJECTIVES We investigated combined and separate effects of high dairy protein intake and vitamin D on body composition and cardiometabolic markers in children. METHODS In a 2 × 2-factorial, randomized trial, 200 white, Danish, 6-8-y-old children substituted 260 g/d dairy in their diet with high-protein (HP; 10 g protein/100 g) or normal-protein (NP; 3.5 g protein/100 g) yogurt and received blinded tablets with 20 µg/d vitamin D3 or placebo for 24 wk during winter. We measured body composition (by DXA), blood pressure, and fasting blood glucose, insulin, C-peptide, and lipids. RESULTS In total, 184 children (92%) completed the study. Baseline median (25th-75th percentile) dairy protein intake was median: 3.7 (25th-75th percentile: 2.5-5.1) energy percentage (E%) and increased to median: 7.2 (25th-75th percentile: 4.7-8.8) E% and median: 4.2 (25th-75th percentile: 3.1-5.3) E% with HP and NP. Mean ± SD serum 25-hydroxyvitamin D concentration changed from 81 ± 17 to 89 ± 18 nmol/L and 48 ± 13 nmol/L with vitamin D and placebo, respectively. There were no combined effects of dairy protein and vitamin D, except for plasma glucose, with the largest increase in the NP-vitamin D group (Pinteraction = 0.005). There were smaller increases in fat mass index (P = 0.04) with HP than with NP, and the same pattern was seen for insulin, HOMA-IR, and C-peptide (all P = 0.06). LDL cholesterol was reduced with vitamin D compared with placebo (P < 0.05). Fat-free mass and blood pressure were unaffected. CONCLUSIONS High compared with normal dairy protein intake hampered an increase in fat mass index. Vitamin D supplementation counteracted the winter decline in 25-hydroxyvitamin D and the increase in LDL cholesterol observed with placebo. This study adds to the sparse evidence on dairy protein in well-nourished children and supports a vitamin D intake of ∼20 µg/d during winter. This trial was registered at clinicaltrials.gov as NCT03956732.
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Affiliation(s)
- Line Thams
- Section for Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Nanna G Stounbjerg
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
| | - Lars G Hvid
- Section for Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Christian Mølgaard
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
| | - Mette Hansen
- Section for Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Camilla T Damsgaard
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark
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31
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da Cruz SP, Cruz S, Pereira S, Saboya C, Lack Veiga JC, Ramalho A. Adequacy and Vitamin D in the Preoperative Period of Roux-en-Y Gastric Bypass, Bariatric Surgery, Can Protect Metabolic Health in Metabolically Healthy and Unhealthy Individuals. Nutrients 2022; 14:402. [PMID: 35276762 PMCID: PMC8839357 DOI: 10.3390/nu14030402] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/10/2022] [Accepted: 01/13/2022] [Indexed: 12/14/2022] Open
Abstract
Evaluating the influence of vitamin D concentrations together with preoperative metabolic phenotypes on remission of chronic noncommunicable diseases (CNCDs) after 6 months of Roux-en-Y gastric bypass (RYGB). Cross-sectional analytical study comprising 30 adult individuals who were assessed preoperatively (T0) and 6 months (T1) after undergoing RYGB. Participants were distributed preoperatively into metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) individuals according to HOMA-IR classification and to the adequacy and inadequacy of vitamin D concentrations in the form of 25(OH)D. All participants were assessed for anthropometric characteristics, biochemical variables, and presence of CNCDs. The statistical program used was the SPSS version 21. In face of vitamin D adequacy and regardless of the metabolic phenotype classification in the preoperative period, the means found for HOMA-IR allowed us to define them as metabolically healthy 6 months after RYGB. Only those with vitamin D inadequacy with the MUHO phenotype showed better results regarding the reduction of glucose that accompanied the shift in serum 25(OH)D concentrations from deficient to insufficient. It is possible that preoperative vitamin D adequacy, even in the presence of an unhealthy phenotype, may contribute to the reduction of dyslipidemia and improvement in cholesterol. It is suggested that preoperative vitamin D adequacy in both phenotypes may have a protective effect on metabolic health.
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Affiliation(s)
- Suelem Pereira da Cruz
- Center for Research on Micronutrients, Federal University of Rio de Janeiro (NPqM/UFRJ), Rio de Janeiro 21941-902, Brazil; (S.C.); (A.R.)
| | - Sabrina Cruz
- Center for Research on Micronutrients, Federal University of Rio de Janeiro (NPqM/UFRJ), Rio de Janeiro 21941-902, Brazil; (S.C.); (A.R.)
| | - Silvia Pereira
- Multidisciplinary Center for Bariatric and Metabolic Surgery, Federal University of Rio de Janeiro (NPqM/UFRJ), Rio de Janeiro 21941-902, Brazil;
| | - Carlos Saboya
- Brazilian Society of Bariatric and Metabolic Surgery, Rio de Janeiro 22280-020, Brazil;
| | | | - Andréa Ramalho
- Center for Research on Micronutrients, Federal University of Rio de Janeiro (NPqM/UFRJ), Rio de Janeiro 21941-902, Brazil; (S.C.); (A.R.)
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32
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Szymczak-Pajor I, Miazek K, Selmi A, Balcerczyk A, Śliwińska A. The Action of Vitamin D in Adipose Tissue: Is There the Link between Vitamin D Deficiency and Adipose Tissue-Related Metabolic Disorders? Int J Mol Sci 2022; 23:956. [PMID: 35055140 PMCID: PMC8779075 DOI: 10.3390/ijms23020956] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 01/09/2022] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing and releasing energy. In obesity, adipose tissue becomes dysfunctional and characterized by hypertrophied adipocytes, increased inflammation, hypoxia, and decreased angiogenesis. Although adipose tissue is one of the major stores of vitamin D, its deficiency is detective in obese subjects. In the presented review, we show how vitamin D regulates numerous processes in adipose tissue and how their dysregulation leads to metabolic disorders. The molecular response to vitamin D in adipose tissue affects not only energy metabolism and adipokine and anti-inflammatory cytokine production via the regulation of gene expression but also genes participating in antioxidant defense, adipocytes differentiation, and apoptosis. Thus, its deficiency disturbs adipocytokines secretion, metabolism, lipid storage, adipogenesis, thermogenesis, the regulation of inflammation, and oxidative stress balance. Restoring the proper functionality of adipose tissue in overweight or obese subjects is of particular importance in order to reduce the risk of developing obesity-related complications, such as cardiovascular diseases and diabetes. Taking into account the results of experimental studies, it seemed that vitamin D may be a remedy for adipose tissue dysfunction, but the results of the clinical trials are not consistent, as some of them show improvement and others no effect of this vitamin on metabolic and insulin resistance parameters. Therefore, further studies are required to evaluate the beneficial effects of vitamin D, especially in overweight and obese subjects, due to the presence of a volumetric dilution of this vitamin among them.
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Affiliation(s)
- Izabela Szymczak-Pajor
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland;
| | - Krystian Miazek
- Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, 15 Wroblewskiego, 93-590 Lodz, Poland;
| | - Anna Selmi
- Department of Molecular Biophysics, University of Lodz, 141/143 Pomorska, 90-236 Lodz, Poland; (A.S.); (A.B.)
| | - Aneta Balcerczyk
- Department of Molecular Biophysics, University of Lodz, 141/143 Pomorska, 90-236 Lodz, Poland; (A.S.); (A.B.)
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland;
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Marziou A, Aubert B, Couturier C, Astier J, Philouze C, Obert P, Landrier JF, Riva C. Combined Beneficial Effect of Voluntary Physical Exercise and Vitamin D Supplementation in Diet-induced Obese C57BL/6J Mice. Med Sci Sports Exerc 2021; 53:1883-1894. [PMID: 33787528 DOI: 10.1249/mss.0000000000002664] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE Physical exercise (PE) combined with nutritional approaches has beneficial effects that are widely advocated to improve metabolic health. Here we used voluntary PE together with vitamin D (VD) supplementation, which has already shown beneficial effects in primary and tertiary prevention in obese mice models, to study their combined additive effects on body weight management, glucose homeostasis, metabolic inflammation, and liver steatosis as key markers of metabolic health. METHODS Ten-week-old male C57BL/6J mice were fed a high-fat/sucrose (HFS) diet for 10 wk, then assigned to a 15-wk intervention period with PE, VD supplementation, or both PE and VD supplementation. Morphological, histological, and molecular phenotype data were characterized. RESULTS The HFS-induced increases in body mass, adiposity, and adipocyte hypertrophy were improved by PE but not by VD supplementation. The HFS-induced inflammation (highlighted by chemokines mRNA levels) in inguinal adipose tissue was decreased by PE and/or VD supplementation. Furthermore, the intervention combining PE and VD showed additive effects on restoring insulin sensitivity and improving hepatic steatosis, as demonstrated through a normalization of size and number of hepatic lipid droplets and triglyceride content and a significant molecular-level decrease in the expression of genes coding for key enzymes in hepatic de novo lipogenesis. CONCLUSIONS Taken together, our data show beneficial effects of combining PE and VD supplementation on obesity-associated comorbidities such as insulin resistance and hepatic disease in mice. This combined exercise-nutritional support strategy could prove valuable in obesity management programs.
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Affiliation(s)
| | | | | | - Julien Astier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, FRANCE
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Tian LQ, Yu YT, Jin MD, Duan HL, Huang G, Zhang ML. Early 1,25-Dihydroxyvitamin D 3 Supplementation Effectively Lowers the Incidence of Type 2 Diabetes Mellitus via Ameliorating Inflammation In KK-A y Mice. J Nutr Sci Vitaminol (Tokyo) 2021; 67:84-90. [PMID: 33952739 DOI: 10.3177/jnsv.67.84] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Few studies have been performed to investigate the effect of vitamin D supplementation and T2DM in type 2 diabetic animal models. The present study aimed to explore the relationship between early 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the incidence of T2DM and determine whether early 1,25(OH)2D3 supplementation was associated with inflammation in KK-Ay mice. The KK-Ay mice were divided into 4 vitamin D treatment groups, the low-dose vitamin D supplementation group (VDS-L, 1.5 μg/kg 1,25(OH)2D3), moderate-dose vitamin D supplementation group (VDS-M, 3.0 μg/kg 1,25(OH)2D3), high-dose vitamin D supplementation group (VDS-H, 6.0 μg/kg 1,25(OH)2D3) and the model control group (MC). C57BL/6J mice were used as the controls. The treatment period lasted for 9 wk. During this treatment period, fasting blood glucose (FBG) level of the mice was measured on a weekly basis. The levels of lipid profile, insulin and inflammation biomarkers were determined after 9 wk of 1,25(OH)2D3 intragastric gavage. After 9 wk of 1,25(OH)2D3 intragastric gavage, FBG level was significantly decreased in the vitamin D treatment groups compared with the MC group. The number of T2DM incidence in the VDS-L group (n=7), VDS-M group (n=5) and VDS-H group (n=3) was lower than those in the MC group (n=10) on week 9. Moreover, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the vitamin D treatment groups were significantly suppressed by 1,25(OH)2D3 administration compared with the MC group. Early 1,25(OH)2D3 supplementation could effectively lower the incidence of T2DM via ameliorating inflammation in KK-Ay mice.
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Affiliation(s)
- Li-Qiang Tian
- Department of Clinical Laboratory, Tianjin Chest Hospital
| | - Yan-Ting Yu
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University
| | - Meng-Di Jin
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University
| | - Hui-Lian Duan
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University
| | - Guowei Huang
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University
| | - Mei-Lin Zhang
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University
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Abstract
PURPOSE OF REVIEW The purpose of this paper is to review the prevalence, pathophysiology, and management of fragile X-associated tremor/ataxia syndrome (FXTAS). RECENT FINDINGS The pathophysiology of FXTAS involves ribonucleic acid (RNA) toxicity due to elevated levels of the premutation-expanded CGG (eoxycytidylate-deoxyguanylate-deoxyguanylate)-repeat FMR1 mRNA, which can sequester a variety of proteins important for neuronal function. A recent analysis of the inclusions in FXTAS demonstrates elevated levels of several proteins, including small ubiquitin-related modifiers 1/2 (SUMO1/2), that target molecules for the proteasome, suggesting that some aspect(s) of proteasomal function may be altered in FXTAS. Recent neuropathological studies show that Parkinson disease and Alzheimer disease can sometimes co-occur with FXTAS. Lewy bodies can be found in 10% of the brains of patients with FXTAS. Microbleeds and iron deposition are also common in the neuropathology, in addition to white matter disease (WMD) and atrophy. SUMMARY The premutation occurs in 1:200 females and 1:400 males. Penetrance for FXTAS increases with age, though lower in females (16%) compared to over 60% of males by age 70. To diagnose FXTAS, an MRI is essential to document the presence of WMD, a primary component of the diagnostic criteria. Pain can be a significant feature of FXTAS and is seen in approximately 50% of patients.
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The association between vitamin D receptor polymorphisms and tissue-specific insulin resistance in human obesity. Int J Obes (Lond) 2021; 45:818-827. [PMID: 33473175 DOI: 10.1038/s41366-021-00744-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 10/27/2020] [Accepted: 01/04/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND/OBJECTIVES To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort. METHODS We included 553 adult obese individuals (mean BMI 34.8 kg/m2), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression. RESULTS None of the VDR polymorphisms were associated with HIRI or MISI. Interestingly, carriers of the G allele of VDR FokI showed higher Adipo-IR (GG + GA 7.8 ± 0.4 vs. AA 5.6 ± 0.5, P = 0.010) and higher systemic FFA (GG + GA: 637.8 ± 13.4 vs. AA: 547.9 ± 24.7 µmol/L, P = 0.011), even after adjustment with age, sex, center, and FM. However, eQTL analysis showed minor to no effect of these genotypes on the transcriptional level in SAT. Also, VDR polymorphisms were not related to changes in body weight and IR as result of dietary intervention (P > 0.05 for all parameters). CONCLUSIONS The VDR Fokl variant is associated with elevated circulating FFA and Adipo-IR at baseline. Nevertheless, minor to no effect of VDR SNPs on the transcriptional level in SAT, indicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.
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Association of serum vitamin D status with development of type 2 diabetes: A retrospective cross-sectional study. CLINICAL NUTRITION OPEN SCIENCE 2021. [DOI: 10.1016/j.nutos.2020.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Park CY, Han SN. The Role of Vitamin D in Adipose Tissue Biology: Adipocyte Differentiation, Energy Metabolism, and Inflammation. J Lipid Atheroscler 2021; 10:130-144. [PMID: 34095008 PMCID: PMC8159757 DOI: 10.12997/jla.2021.10.2.130] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/07/2021] [Accepted: 01/29/2021] [Indexed: 12/27/2022] Open
Abstract
Adipose tissue is composed of diverse cell types and plays a major role in energy homeostasis and inflammation at the local and systemic levels. Adipose tissue serves as the main site for vitamin D storage and is among the most important extraskeletal targets of vitamin D which can modulate multiple aspects of adipose tissue biology. Vitamin D may exert inhibitory or stimulatory effects on adipocyte differentiation depending on cell type, stage of differentiation, and the treatment time point. Moreover, vitamin D controls energy metabolism in adipose tissue by affecting fatty acid oxidation, expression of uncoupling proteins, insulin resistance, and adipokine production. Adipose tissue inflammation can have a significant impact on the metabolic disorders often associated with obesity, and vitamin D can modulate the inflammatory response of immune cells and adipocytes within the adipose tissue. This review discusses the role of adipose tissue in vitamin D metabolism, as well as the regulatory role of vitamin D in adipocyte differentiation, adipose tissue energy metabolism, and inflammation, thereby providing insights into the importance of vitamin D in adipose tissue biology.
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Affiliation(s)
- Chan Yoon Park
- Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.,Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Korea
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Nimitphong H, Guo W, Holick MF, Fried SK, Lee MJ. Vitamin D Inhibits Adipokine Production and Inflammatory Signaling Through the Vitamin D Receptor in Human Adipocytes. Obesity (Silver Spring) 2021; 29:562-568. [PMID: 33624437 DOI: 10.1002/oby.23109] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/01/2020] [Accepted: 12/05/2020] [Indexed: 11/10/2022]
Abstract
OBJECTIVE The purpose of this study was to investigate the effects of vitamin D on adipokine expression and inflammation in human adipose tissues and adipocytes and evaluate the molecular mechanisms involved. METHODS Omental and abdominal subcutaneous human adipose tissues were treated with 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), and adipokine levels were measured. Vitamin D effects were measured with or without dexamethasone because glucocorticoids are known to affect vitamin D actions. Using RNA interference, we examined whether the vitamin D receptor (VDR) mediated vitamin D actions on adipokine expression and inflammatory signaling pathways in human adipocytes. RESULTS mRNA levels and secretion of leptin and IL-6 were suppressed by 1,25(OH)2 D3 in omental adipose tissues. Cotreatment with dexamethasone did not affect these inhibitory actions but partially blocked CYP24A1 induction. Similar results were observed in the subcutaneous depot. In addition, 1,25(OH)2 D3 suppressed leptin and IL-6 expression as well as nuclear factor-κB and extracellular signal-regulated kinase-1/2 phosphorylation in human adipocytes. Adipokine expression also was decreased by 25-hydroxyvitamin D3 (25(OH)D3 ), but not vitamin D3 . Knockdown of VDR increased the inflammatory signaling activity in the control condition and blocked the inhibitory effects of 1,25(OH)2 D3 on adipokine and inflammatory signaling pathways. CONCLUSION Vitamin D acts through VDR to inhibit inflammatory pathways and adipokine expression in human adipocytes. Increasing vitamin D status may ameliorate obesity-associated metabolic complications by decreasing adipose tissue inflammation.
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Affiliation(s)
- Hataikarn Nimitphong
- Department of Medicine, Section of Endocrinology and Metabolism, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Weimin Guo
- Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Michael F Holick
- Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Susan K Fried
- Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
- Diabetes Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Mi-Jeong Lee
- Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA
- Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, Hawaii, USA
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Maresin 1 regulates insulin signaling in human adipocytes as well as in adipose tissue and muscle of lean and obese mice. J Physiol Biochem 2020; 77:167-173. [PMID: 33206345 DOI: 10.1007/s13105-020-00775-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 11/04/2020] [Indexed: 02/08/2023]
Abstract
Maresin 1 (MaR1) is a DHA-derived pro-resolving lipid mediator. The present study aimed to characterize the ability of MaR1 to prevent the alterations induced by TNF-α on insulin actions in glucose uptake and Akt phosphorylation in cultured human adipocytes from overweight/obese subjects, as well as to investigate the effects of MaR1 acute and chronic administration on Akt phosphorylation in absence/presence of insulin in white adipose tissue (WAT) and skeletal muscle from lean and diet-induced obese (DIO) mice. MaR1 (0.1 nM) prevented the inhibitory effect of TNF-α on insulin-stimulated 2-Deoxy-D-glucose uptake and Akt phosphorylation in human adipocytes. Acute treatment with MaR1 (50 μg/kg, 3 h, i.p.) induced Akt phosphorylation in WAT and skeletal muscle of lean mice. However, MaR1 did not further increase the stimulatory effect of insulin on Akt activation. Interestingly, intragastric chronic treatment with MaR1 (50 μg/kg, 10 days) in DIO mice reduced the hyperglycemia induced by the high fat diet (HFD) and improved systemic insulin sensitivity. In parallel, MaR1 partially restored the impaired insulin response in skeletal muscle of DIO mice and reversed HFD-induced lower Akt phosphorylation in WAT in non-insulin-stimulated DIO mice while did not restore the defective Akt activation in response to acute insulin observed in DIO mice. Our results suggest that MaR1 attenuates the impaired insulin signaling and glucose uptake induced by proinflammatory cytokines. Moreover, the current data support that MaR1 treatment could be useful to reduce the hyperglycemia and the insulin resistance associated to obesity, at least in part by improving Akt signaling.
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Seipelt EM, Tourniaire F, Couturier C, Astier J, Loriod B, Vachon H, Pucéat M, Mounien L, Landrier JF. Prenatal maternal vitamin D deficiency sex-dependently programs adipose tissue metabolism and energy homeostasis in offspring. FASEB J 2020; 34:14905-14919. [PMID: 32924159 DOI: 10.1096/fj.201902924rr] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 08/24/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023]
Abstract
In utero environment is crucial to ensure normal development of the fetus and to program metabolic health throughout the life. Beside macronutrients, the role of micronutrients, including vitamin D, begins to be explore. The aim of this study was to decipher the impact of maternal vitamin D deficiency (VDD), in normal and high-fat (HF) diet context, on adipose tissue metabolism and energy homeostasis in offspring, considering sex-specific responses. Body weight, energy expenditure, and spontaneous activity was differential impacted in juvenile male and female offspring born from VDD mice. In adulthood, a HF diet combined with maternal VDD disrupted glucose homeostasis and adiposity in male offspring but not in females. Such phenotypes were associated to different transcriptomic profiles in adipose tissue, which could be related to differential modulation of plasma 17β-estradiol concentrations. Thus, maternal VDD sex-dependently modulated metabolic fate of the offspring, especially when associated with HF diet in adulthood.
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Affiliation(s)
- Eva M Seipelt
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,Aix-Marseille Université, MMG, INSERM U1251, Marseille, France
| | - Franck Tourniaire
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,CriBioM, Criblage Biologique Marseille, Faculté de médecine de la Timone, Marseille, France
| | | | - Julien Astier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Béatrice Loriod
- Aix-Marseille Université, TGML, TAGC, INSERM, Marseille, France
| | - Hortense Vachon
- Aix-Marseille Université, TGML, TAGC, INSERM, Marseille, France
| | - Michel Pucéat
- Aix-Marseille Université, MMG, INSERM U1251, Marseille, France
| | - Lourdes Mounien
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France
| | - Jean-François Landrier
- Aix-Marseille Université, C2VN, INRAE, INSERM, Marseille, France.,CriBioM, Criblage Biologique Marseille, Faculté de médecine de la Timone, Marseille, France
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The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders. Int J Mol Sci 2020; 21:ijms21186644. [PMID: 32932777 PMCID: PMC7554927 DOI: 10.3390/ijms21186644] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
Numerous studies have shown that vitamin D deficiency is very common in modern societies and is perceived as an important risk factor in the development of insulin resistance and related diseases such as obesity and type 2 diabetes (T2DM). While it is generally accepted that vitamin D is a regulator of bone homeostasis, its ability to counteract insulin resistance is subject to debate. The goal of this communication is to review the molecular mechanism by which vitamin D reduces insulin resistance and related complications. The university library, PUBMED, and Google Scholar were searched to find relevant studies to be summarized in this review article. Insulin resistance is accompanied by chronic hyperglycaemia and inflammation. Recent studies have shown that vitamin D exhibits indirect antioxidative properties and participates in the maintenance of normal resting ROS level. Appealingly, vitamin D reduces inflammation and regulates Ca2+ level in many cell types. Therefore, the beneficial actions of vitamin D include diminished insulin resistance which is observed as an improvement of glucose and lipid metabolism in insulin-sensitive tissues.
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Vitamin D serum levels in patients with migraine: A meta-analysis. Rev Neurol (Paris) 2020; 176:560-570. [DOI: 10.1016/j.neurol.2019.12.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 11/29/2019] [Accepted: 12/10/2019] [Indexed: 01/03/2023]
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Cheung WW, Ding W, Hoffman HM, Wang Z, Hao S, Zheng R, Gonzalez A, Zhan JY, Zhou P, Li S, Esparza MC, Lieber RL, Mak RH. Vitamin D ameliorates adipose browning in chronic kidney disease cachexia. Sci Rep 2020; 10:14175. [PMID: 32843714 PMCID: PMC7447759 DOI: 10.1038/s41598-020-70190-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 07/21/2020] [Indexed: 12/15/2022] Open
Abstract
Patients with chronic kidney disease (CKD) are often 25(OH)D3 and 1,25(OH)2D3 insufficient. We studied whether vitamin D repletion could correct aberrant adipose tissue and muscle metabolism in a mouse model of CKD-associated cachexia. Intraperitoneal administration of 25(OH)D3 and 1,25(OH)2D3 (75 μg/kg/day and 60 ng/kg/day respectively for 6 weeks) normalized serum concentrations of 25(OH)D3 and 1,25(OH)2D3 in CKD mice. Vitamin D repletion stimulated appetite, normalized weight gain, and improved fat and lean mass content in CKD mice. Vitamin D supplementation attenuated expression of key molecules involved in adipose tissue browning and ameliorated expression of thermogenic genes in adipose tissue and skeletal muscle in CKD mice. Furthermore, repletion of vitamin D improved skeletal muscle fiber size and in vivo muscle function, normalized muscle collagen content and attenuated muscle fat infiltration as well as pathogenetic molecular pathways related to muscle mass regulation in CKD mice. RNAseq analysis was performed on the gastrocnemius muscle. Ingenuity Pathway Analysis revealed that the top 12 differentially expressed genes in CKD were correlated with impaired muscle and neuron regeneration, enhanced muscle thermogenesis and fibrosis. Importantly, vitamin D repletion normalized the expression of those 12 genes in CKD mice. Vitamin D repletion may be an effective therapeutic strategy for adipose tissue browning and muscle wasting in CKD patients.
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MESH Headings
- Adipocytes, Beige/drug effects
- Adipocytes, Beige/metabolism
- Adipocytes, Brown/metabolism
- Adipocytes, White/metabolism
- Animals
- Cachexia/drug therapy
- Cachexia/etiology
- Cachexia/physiopathology
- Calcifediol/blood
- Calcifediol/deficiency
- Calcifediol/pharmacology
- Calcifediol/therapeutic use
- Calcitriol/blood
- Calcitriol/deficiency
- Calcitriol/pharmacology
- Calcitriol/therapeutic use
- Disease Models, Animal
- Eating/drug effects
- Fibrosis/genetics
- Gene Expression Regulation/drug effects
- Hand Strength
- Mice
- Mice, Inbred C57BL
- Muscle Fibers, Skeletal/drug effects
- Muscle Fibers, Skeletal/pathology
- Nephrectomy
- Parathyroid Hormone/blood
- RNA, Messenger/biosynthesis
- Renal Insufficiency, Chronic/blood
- Renal Insufficiency, Chronic/complications
- Renal Insufficiency, Chronic/drug therapy
- Rotarod Performance Test
- Sequence Analysis, RNA
- Thermogenesis/drug effects
- Weight Gain/drug effects
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Affiliation(s)
- Wai W Cheung
- Pediatric Nephrology, Rady Children's Hospital San Diego, University of California, San Diego, USA
| | - Wei Ding
- Division of Nephrology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Hal M Hoffman
- Department of Pediatrics, University of California, San Diego, USA
| | - Zhen Wang
- Department of Pediatrics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Sheng Hao
- Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ronghao Zheng
- Department of Pediatrics, Hubei Maternal and Child Health Hospital, Wuhan, China
| | - Alex Gonzalez
- Pediatric Nephrology, Rady Children's Hospital San Diego, University of California, San Diego, USA
| | - Jian-Ying Zhan
- Children's Hospital, Zhejiang University, Hangzhou, China
| | - Ping Zhou
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shiping Li
- College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China
| | - Mary C Esparza
- Department of Orthopedic Surgery, University of California, San Diego, USA
| | - Richard L Lieber
- Shirley Ryan AbilityLab and Northwestern University, Chicago, USA
| | - Robert H Mak
- Pediatric Nephrology, Rady Children's Hospital San Diego, University of California, San Diego, USA.
- Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, MC 0831, La Jolla, CA, 92093-0831, USA.
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Nimitphong H, Park E, Lee MJ. Vitamin D regulation of adipogenesis and adipose tissue functions. Nutr Res Pract 2020; 14:553-567. [PMID: 33282119 PMCID: PMC7683208 DOI: 10.4162/nrp.2020.14.6.553] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/03/2020] [Accepted: 07/16/2020] [Indexed: 12/11/2022] Open
Abstract
Vitamin D insufficiency is associated with obesity and its related metabolic diseases. Adipose tissues store and metabolize vitamin D and expression levels of vitamin D metabolizing enzymes are known to be altered in obesity. Sequestration of vitamin D in large amount of adipose tissues and low vitamin D metabolism may contribute to the vitamin D inadequacy in obesity. Vitamin D receptor is expressed in adipose tissues and vitamin D regulates multiple aspects of adipose biology including adipogenesis as well as metabolic and endocrine function of adipose tissues that can contribute to the high risk of metabolic diseases in vitamin D insufficiency. We will review current understanding of vitamin D regulation of adipose biology focusing on vitamin D modulation of adiposity and adipose tissue functions as well as the molecular mechanisms through which vitamin D regulates adipose biology. The effects of supplementation or maintenance of vitamin D on obesity and metabolic diseases are also discussed.
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Affiliation(s)
- Hataikarn Nimitphong
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Eunmi Park
- Department of Food and Nutrition, Hannam University, Daejeon 34430, Korea
| | - Mi-Jeong Lee
- Department of Human Nutrition, Food and Animal Sciences, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, HI 96822, USA
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Griffith RJ, Alsweiler J, Moore AE, Brown S, Middleton P, Shepherd E, Crowther CA. Interventions to prevent women from developing gestational diabetes mellitus: an overview of Cochrane Reviews. Cochrane Database Syst Rev 2020; 6:CD012394. [PMID: 32526091 PMCID: PMC7388385 DOI: 10.1002/14651858.cd012394.pub3] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The prevalence of gestational diabetes mellitus (GDM) is increasing, with approximately 15% of pregnant women affected worldwide, varying by country, ethnicity and diagnostic thresholds. There are associated short- and long-term health risks for women and their babies. OBJECTIVES We aimed to summarise the evidence from Cochrane systematic reviews on the effects of interventions for preventing GDM. METHODS We searched the Cochrane Database of Systematic Reviews (6 August 2019) with key words 'gestational diabetes' OR 'GDM' to identify reviews pre-specifying GDM as an outcome. We included reviews of interventions in women who were pregnant or planning a pregnancy, irrespective of their GDM risk status. Two overview authors independently assessed eligibility, extracted data and assessed quality of evidence using ROBIS and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm (GRADE moderate- or high-quality evidence with a confidence interval (CI) that did not cross the line of no effect); clear evidence of no effect or equivalence (GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect); possible benefit or harm (low-quality evidence with a CI that did not cross the line of no effect or GRADE moderate- or high-quality evidence with a wide CI); or unknown benefit or harm (GRADE low-quality evidence with a wide CI or very low-quality evidence). MAIN RESULTS We included 11 Cochrane Reviews (71 trials, 23,154 women) with data on GDM. Nine additional reviews pre-specified GDM as an outcome, but did not identify GDM data in included trials. Ten of the 11 reviews were judged to be at low risk of bias and one review at unclear risk of bias. Interventions assessed included diet, exercise, a combination of diet and exercise, dietary supplements, pharmaceuticals, and management of other health problems in pregnancy. The quality of evidence ranged from high to very low. Diet Unknown benefit or harm: there was unknown benefit or harm of dietary advice versus standard care, on the risk of GDM: risk ratio (RR) 0.60, 95% CI 0.35 to 1.04; 5 trials; 1279 women; very low-quality evidence. There was unknown benefit or harm of a low glycaemic index diet versus a moderate-high glycaemic index diet on the risk of GDM: RR 0.91, 95% CI 0.63 to 1.31; 4 trials; 912 women; low-quality evidence. Exercise Unknown benefit or harm: there was unknown benefit or harm for exercise interventions versus standard antenatal care on the risk of GDM: RR 1.10, 95% CI 0.66 to 1.84; 3 trials; 826 women; low-quality evidence. Diet and exercise combined Possible benefit: combined diet and exercise interventions during pregnancy versus standard care possibly reduced the risk of GDM: RR 0.85, 95% CI 0.71 to 1.01; 19 trials; 6633 women; moderate-quality evidence. Dietary supplements Clear evidence of no effect: omega-3 fatty acid supplementation versus none in pregnancy had no effect on the risk of GDM: RR 1.02, 95% CI 0.83 to 1.26; 12 trials; 5235 women; high-quality evidence. Possible benefit: myo-inositol supplementation during pregnancy versus control possibly reduced the risk of GDM: RR 0.43, 95% CI 0.29 to 0.64; 3 trials; 502 women; low-quality evidence. Possible benefit: vitamin D supplementation versus placebo or control in pregnancy possibly reduced the risk of GDM: RR 0.51, 95% CI 0.27 to 0.97; 4 trials; 446 women; low-quality evidence. Unknown benefit or harm: there was unknown benefit or harm of probiotic with dietary intervention versus placebo with dietary intervention (RR 0.37, 95% CI 0.15 to 0.89; 1 trial; 114 women; very low-quality evidence), or probiotic with dietary intervention versus control (RR 0.38, 95% CI 0.16 to 0.92; 1 trial; 111 women; very low-quality evidence) on the risk of GDM. There was unknown benefit or harm of vitamin D + calcium supplementation versus placebo (RR 0.33, 95% CI 0.01 to 7.84; 1 trial; 54 women; very low-quality evidence) or vitamin D + calcium + other minerals versus calcium + other minerals (RR 0.42, 95% CI 0.10 to 1.73; 1 trial; 1298 women; very low-quality evidence) on the risk of GDM. Pharmaceutical Possible benefit: metformin versus placebo given to obese pregnant women possibly reduced the risk of GDM: RR 0.85, 95% CI 0.61 to 1.19; 3 trials; 892 women; moderate-quality evidence. Unknown benefit or harm:eight small trials with low- to very low-quality evidence showed unknown benefit or harm for heparin, aspirin, leukocyte immunisation or IgG given to women with a previous stillbirth on the risk of GDM. Management of other health issues Clear evidence of no effect: universal versus risk based screening of pregnant women for thyroid dysfunction had no effect on the risk of GDM: RR 0.93, 95% CI 0.70 to 1.25; 1 trial; 4516 women; moderate-quality evidence. Unknown benefit or harm: there was unknown benefit or harm of using fractional exhaled nitrogen oxide versus a clinical algorithm to adjust asthma therapy on the risk of GDM: RR 0.74, 95% CI 0.31 to 1.77; 1 trial; 210 women; low-quality evidence. There was unknown benefit or harm of pharmacist led multidisciplinary approach to management of maternal asthma versus standard care on the risk of GDM: RR 5.00, 95% CI 0.25 to 99.82; 1 trial; 58 women; low-quality evidence. AUTHORS' CONCLUSIONS No interventions to prevent GDM in 11 systematic reviews were of clear benefit or harm. A combination of exercise and diet, supplementation with myo-inositol, supplementation with vitamin D and metformin were of possible benefit in reducing the risk of GDM, but further high-quality evidence is needed. Omega-3-fatty acid supplementation and universal screening for thyroid dysfunction did not alter the risk of GDM. There was insufficient high-quality evidence to establish the effect on the risk of GDM of diet or exercise alone, probiotics, vitamin D with calcium or other vitamins and minerals, interventions in pregnancy after a previous stillbirth, and different asthma management strategies in pregnancy. There is a lack of trials investigating the effect of interventions prior to or between pregnancies on risk of GDM.
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Affiliation(s)
- Rebecca J Griffith
- Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand
| | - Jane Alsweiler
- Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand
| | - Abigail E Moore
- Liggins Institute, The University of Auckland, Auckland, New Zealand
| | - Stephen Brown
- School of Interprofessional Health Studies, Auckland University of Technology, Auckland, New Zealand
| | - Philippa Middleton
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Emily Shepherd
- Robinson Research Institute, Discipline of Obstetrics and Gynaecology, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
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Tran V, De Silva TM, Sobey CG, Lim K, Drummond GR, Vinh A, Jelinic M. The Vascular Consequences of Metabolic Syndrome: Rodent Models, Endothelial Dysfunction, and Current Therapies. Front Pharmacol 2020; 11:148. [PMID: 32194403 PMCID: PMC7064630 DOI: 10.3389/fphar.2020.00148] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Accepted: 02/04/2020] [Indexed: 12/30/2022] Open
Abstract
Metabolic syndrome is characterized by visceral obesity, dyslipidemia, hyperglycemia and hypertension, and affects over one billion people. Independently, the components of metabolic syndrome each have the potential to affect the endothelium to cause vascular dysfunction and disrupt vascular homeostasis. Rodent models of metabolic syndrome have significantly advanced our understanding of this multifactorial condition. In this mini-review we compare the currently available rodent models of metabolic syndrome and consider their limitations. We also discuss the numerous mechanisms by which metabolic abnormalities cause endothelial dysfunction and highlight some common pathophysiologies including reduced nitric oxide production, increased reactive oxygen species and increased production of vasoconstrictors. Additionally, we explore some of the current therapeutics for the comorbidities of metabolic syndrome and consider how these benefit the vasculature.
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Affiliation(s)
- Vivian Tran
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - T Michael De Silva
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - Christopher G Sobey
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - Kyungjoon Lim
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - Grant R Drummond
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - Antony Vinh
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
| | - Maria Jelinic
- Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
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Hauger H, Laursen RP, Ritz C, Mølgaard C, Lind MV, Damsgaard CT. Effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2020; 59:873-884. [DOI: 10.1007/s00394-019-02150-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 11/18/2019] [Indexed: 02/06/2023]
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Effects of 1,25-dihydroxyvitamin D3 on the Inflammatory Responses of Stromal Vascular Cells and Adipocytes from Lean and Obese Mice. Nutrients 2020; 12:nu12020364. [PMID: 32019160 PMCID: PMC7071143 DOI: 10.3390/nu12020364] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/27/2020] [Accepted: 01/28/2020] [Indexed: 02/06/2023] Open
Abstract
Vitamin D status has been implicated in obesity and adipose tissue inflammation. In the present study, we explored the effects of dietary vitamin D supplementation on adipose tissue inflammation and immune cell population, and the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) treatment on pro-inflammatory cytokine production by stromal vascular cells (SVCs) and adipocytes in lean and high-fat diet-induced obese mice. The results show that epididymal fat Mcp-1 and Rantes mRNA levels, which were higher in obese mice compared with lean mice, were significantly down-regulated by vitamin D supplementation. While obese mice had higher numbers of macrophages and natural killer (NK) cells within adipose tissue, these remained unaltered by vitamin D supplementation. In accordance with these in vivo findings, the in vitro 1,25(OH)2D3 treatment decreased IL-6, MCP-1, and IL-1β production by SVCs from obese mice, but not by adipocytes. In addition, 1,25(OH)2D3 treatment significantly decreased Tlr2 expression and increased mRNA levels of Iκba and Dusp1 in SVCs. These findings suggest that vitamin D supplementation attenuates inflammatory response in adipose tissue, especially in SVCs, possibly through inhibiting NF-κB and MAPK signaling pathways in SVCs but not by the inhibition of macrophage infiltration.
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Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice. Nutrients 2020; 12:nu12020342. [PMID: 32012987 PMCID: PMC7071313 DOI: 10.3390/nu12020342] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 01/24/2020] [Accepted: 01/27/2020] [Indexed: 02/07/2023] Open
Abstract
The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.
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