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Orioli L, Thissen JP. Myokines as potential mediators of changes in glucose homeostasis and muscle mass after bariatric surgery. Front Endocrinol (Lausanne) 2025; 16:1554617. [PMID: 40171198 PMCID: PMC11958187 DOI: 10.3389/fendo.2025.1554617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 02/28/2025] [Indexed: 04/03/2025] Open
Abstract
Myokines are bioactive peptides released by skeletal muscle. Myokines exert auto-, para-, or endocrine effects, enabling them to regulate many aspects of metabolism in various tissues. However, the contribution of myokines to the dramatic changes in glucose homeostasis and muscle mass induced by bariatric surgery has not been established. Our review highlights that myokines such as brain-derived neurotrophic factor (BDNF), meteorin-like protein (Metrnl), secreted protein acidic and rich in cysteine (SPARC), apelin (APLN) and myostatin (MSTN) may mediate changes in glucose homeostasis and muscle mass after bariatric surgery. Our review also identifies myonectin as an interesting candidate for future studies, as this myokine may regulate lipid metabolism and muscle mass after bariatric surgery. These myokines may provide novel therapeutic targets and biomarkers for obesity, type 2 diabetes and sarcopenia.
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Affiliation(s)
- Laura Orioli
- Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
- Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jean-Paul Thissen
- Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, UCLouvain, Brussels, Belgium
- Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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Butler AE, Nandakumar M, Sathyapalan T, Brennan E, Atkin SL. Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Their Ratios in Women with Polycystic Ovary Syndrome and Healthy Controls. Int J Mol Sci 2025; 26:321. [PMID: 39796177 PMCID: PMC11720512 DOI: 10.3390/ijms26010321] [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: 12/06/2024] [Revised: 12/23/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025] Open
Abstract
Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p < 0.0001, p < 0.005, p < 0.04, p < 0.05, p < 0.0001, and p < 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p < 0.01), MMP-1 (p < 0.05), MMP-2 (p < 0.05), MMP-10 (p < 0.005), MMP-12 (p < 0.005), ADAM-9 (p < 0.05), and IGFBP-1 (p < 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9/TIMP-1, MMP-9/TIMP-2, and MMP-9/TIMP-3 ratios were higher in the PCOS group (p < 0.01), whilst MMP-17/TIMP-1 and MMP-17/TIMP-2 were lower (p = 0.01). MMP-2/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p < 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9/TIMP ratios suggests MMP-9 overactivity in PCOS.
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Affiliation(s)
- Alexandra E. Butler
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Manjula Nandakumar
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK;
| | - Edwina Brennan
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
| | - Stephen L. Atkin
- Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain; (M.N.); (E.B.); (S.L.A.)
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Gentile JKDA, Migliore R, Waisberg J, Ribeiro Junior MAF. The Influence of Bariatric Surgery on Matrix Metalloproteinase Plasma Levels in Patients with Type 2 Diabetes Mellitus. Biomolecules 2024; 14:1633. [PMID: 39766340 PMCID: PMC11727344 DOI: 10.3390/biom14121633] [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: 10/18/2024] [Revised: 12/15/2024] [Accepted: 12/18/2024] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Bariatric surgery is a safe and effective procedure for treating obesity and metabolic conditions such as type 2 diabetes mellitus (T2DM). Remodeling of the extracellular matrix (ECM) supports adipose tissue expansion and its metabolic activity, where matrix metalloproteinases (MMPs) play a key role in ECM regulation. The MMPs, particularly MMP-2 and MMP-9, are elevated in patients with morbid obesity, metabolic syndrome, and T2DM. OBJECTIVES To evaluate the effect of weight loss in bariatric surgery patients using oxidative stress markers and to compare MMP levels in patients undergoing bariatric surgery. METHODS This was a prospective, controlled study including 45 morbidly obese patients with T2DM (BMI > 35 kg/m2) who underwent RYGB (n = 24) or VG (n = 21). Weight loss was assessed through anthropometric measurements (weight, height, BMI). MMP-2 and MMP-9 levels were measured preoperatively and at 3 and 12 months postoperatively. RESULTS Significant and sustained weight loss was observed after surgery in both groups, with reductions in BMI. MMP-2 and MMP-9 levels decreased significantly after one year of follow-up. CONCLUSIONS Bariatric surgery is an effective long-term intervention for weight loss and associated comorbidities, including T2DM. MMP-2 and MMP-9 proved to be effective markers of extracellular matrix remodeling, with significant reductions following surgery.
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Affiliation(s)
| | - Renato Migliore
- Department of Surgery, Hospital São Camilo, São Paulo 02401-200, SP, Brazil;
| | - Jaques Waisberg
- Department of Surgery, ABC Medical School, Santo André 09060-870, SP, Brazil;
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Lempicki MD, Garrigues RJ, Zeczycki TN, Garcia BL, Harris TE, Meher AK. Matrix Metalloproteinase-2 as a novel regulator of glucose utilization by adipocytes. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.12.09.626845. [PMID: 39713289 PMCID: PMC11661172 DOI: 10.1101/2024.12.09.626845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Glucose transporter 4 (GLUT4) expression on white adipocytes is critical for absorbing excess blood glucose, failure of which promotes hyperglycemia. Matrix metalloproteinases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, and surprisingly, it is unknown if they can directly target GLUT4 on the adipocyte surface and impair glucose absorption. We identified MMP2 as the highly active gelatinase, a class of MMP, in the gonadal WAT of high-fat diet-induced obese mice. In vitro, metabolic studies in 3T3-L1 adipocytes revealed MMP2 attenuated glucose absorption and glycolysis, which were recovered by an MMP2 inhibitor. In silico structural analysis using AlphaFold identified a putative MMP2 cleavage site on the extracellular domain of GLUT4. Further, in a substrate competition assay, a peptide mimicking the MMP2 cleavage motif on GLUT4 attenuated the cleavage of an MMP substrate by MMP2. Altogether, our results suggest a novel mechanism of impaired glucose absorption by adipocytes, which may contribute to hyperglycemia during obesity.
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Affiliation(s)
- Melissa D. Lempicki
- Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States
| | - Ryan J. Garrigues
- Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States
| | - Tonya N. Zeczycki
- Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States
| | - Brandon L. Garcia
- Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, United States
| | - Thurl E. Harris
- Department of Pharmacology, University of Virginia, Charlottesville, VA 22903, United States
| | - Akshaya K. Meher
- Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States
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Toba H, Takai S. Exploring the roles of SPARC as a proinflammatory factor and its potential as a novel therapeutic target against cardiovascular disease. Am J Physiol Heart Circ Physiol 2024; 327:H1174-H1186. [PMID: 39269452 DOI: 10.1152/ajpheart.00565.2024] [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: 08/15/2024] [Revised: 09/09/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024]
Abstract
Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of patients with CVD continues to increase despite extensive research and developments in this field. Chronic inflammation is a pivotal pathological component of CVD, and unveiling new proinflammatory factors will help devise novel preventive and therapeutic strategies. The extracellular matrix (ECM) not only provides structural support between cells but also contributes to cellular functions. Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein that is particularly induced during development and tissue remodeling. A proinflammatory role for SPARC has been demonstrated in various animal models, such as in the lipopolysaccharide-induced footpad model and dextran sodium sulfate-induced colitis model. Recent clinical studies reported a positive correlation between elevated plasma SPARC levels and hypertension, obesity, and the inflammatory marker high-sensitive C-reactive protein. In addition, SPARC gene deletion attenuates the cardiac injury induced by aging, myocardial infarction, and pressure load, suggesting that SPARC has deleterious effects on CVD. This review summarizes the regulatory and proinflammatory mechanisms of SPARC on CVD, chronic kidney disease (CKD), and cerebrovascular disease and discusses the rationale behind measuring SPARC as a biomarker of CVD and the effects of inhibition of SPARC in the prevention and treatment of CVD.
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Affiliation(s)
- Hiroe Toba
- Division of Pathological Sciences, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan
- Department of Pharmacology, Educational Foundation of Osaka Medical and Pharmacological University, Takatsuki, Japan
| | - Shinji Takai
- Department of Pharmacology, Educational Foundation of Osaka Medical and Pharmacological University, Takatsuki, Japan
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Engin A. Bariatric Surgery in Obesity: Metabolic Quality Analysis and Comparison of Surgical Options. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:697-726. [PMID: 39287870 DOI: 10.1007/978-3-031-63657-8_24] [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: 09/19/2024]
Abstract
Obesity is a constantly growing health problem which reduces quality of life and life expectancy. Bariatric surgery (BS) for obesity is considered when all other conservative treatment modalities have failed. Comparison of the multidisciplinary programs with BS regarding to the weight loss showed that substantial and durable weight reduction have been achieved only with bariatric surgical treatments. Although laparoscopic sleeve gastrectomy is the most popular BS, it has high long-term failure rates, and it is claimed that one of every three patients will undergo another bariatric procedure within a 10-year period. Although BS provides weight loss and improvement of metabolic comorbidities, in long-term follow-up, weight gain is observed in half of the patients, while decrease in bone mass and nutritional deficiencies occur in up to 90%. Moreover, despite significant weight loss, several psychological aspects of patients are worsened in comparison to preoperative levels. Nearly one-fifth of postoperative patients with "Loss-of-eating control" meet food addiction criteria. Therefore, the benefits of weight loss following bariatric procedures alone are still debated in terms of the proinflammatory and metabolic profile of obesity.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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Ghanemi A, Mac-Way F. Obesity and Bone Mineral Density Protection Paradox in Chronic Kidney Disease: Secreted Protein Acidic and Rich in Cysteine as a Piece of the Puzzle? Life (Basel) 2023; 13:2172. [PMID: 38004312 PMCID: PMC10672555 DOI: 10.3390/life13112172] [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: 09/07/2023] [Revised: 10/08/2023] [Accepted: 10/31/2023] [Indexed: 11/26/2023] Open
Abstract
Obesity is a health condition that represents a risk factor for numerous diseases and complications. However, obesity might also have-to some extent-some "benefits" in certain situations. This includes potential bone protection in patients suffering from chronic kidney disease. In an attempt to explain such a paradox, we highlight secreted protein acidic and rich in cysteine (SPARC) as a hypothetical mediator of this protection. Indeed, SPARC properties provide a logical rationale to describe such bone protection via its overexpression combined with its calcium-binding and collagen-binding properties. We believe that exploring such hypotheses could open new doors to elucidate unknown pathways towards developing a new generation of molecular therapies.
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Affiliation(s)
- Abdelaziz Ghanemi
- Endocrinology and Nephrology Axis, L’Hôtel-Dieu de Québec Hospital, CHU de Québec Research Center, Quebec, QC G1R 2J6, Canada;
- Department of Medicine, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada
| | - Fabrice Mac-Way
- Endocrinology and Nephrology Axis, L’Hôtel-Dieu de Québec Hospital, CHU de Québec Research Center, Quebec, QC G1R 2J6, Canada;
- Department of Medicine, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada
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Atorrasagasti C, Onorato AM, Mazzolini G. The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease. J Physiol Biochem 2023; 79:815-831. [PMID: 36018492 DOI: 10.1007/s13105-022-00913-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/18/2022] [Indexed: 11/28/2022]
Abstract
Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix glycoprotein with pleiotropic functions, which is expressed in adipose, hepatic, muscular, and pancreatic tissue. Particularly, several studies demonstrated that SPARC is an important player in the context of obesity, diabetes, and fatty liver disease including advanced hepatic fibrosis and hepatocellular carcinoma. Evidence in murine and human samples indicates that SPARC is involved in adipogenesis, cellular metabolism, extracellular matrix modulation, glucose and lipid metabolism, among others. Furthermore, studies in SPARC knockout mouse model showed that SPARC contributes to adipose tissue formation, non-alcoholic fatty liver disease (NAFLD), and diabetes. Hence, SPARC may represent a novel and interesting target protein for future therapeutic interventions or a biomarker of disease progression. This review summarizes the role of SPARC in the pathophysiology of obesity, and extensively revised SPARC functions in physiological and pathological adipose tissue deposition, muscle metabolism, liver, and diabetes-related pathways.
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Affiliation(s)
- Catalina Atorrasagasti
- Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Instituto de Investigaciones en Medicina Traslacional, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina.
| | - Agostina M Onorato
- Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Instituto de Investigaciones en Medicina Traslacional, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina
| | - Guillermo Mazzolini
- Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Instituto de Investigaciones en Medicina Traslacional, CONICET- Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina.
- Liver Unit, Hospital Universitario Austral, Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires, Argentina.
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Chaiyasoot K, Khumkhana N, Deekum W, Chaichana C, Taweerutchana V, Srisuworanan N, Pramyothin P. Alteration of BDNF, SPARC, FGF-21, and GDF-15 circulating levels after 1 year of anti-obesity treatments and their association with 1-year weight loss. Endocrine 2023; 82:57-68. [PMID: 37436597 PMCID: PMC10462550 DOI: 10.1007/s12020-023-03435-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/16/2023] [Indexed: 07/13/2023]
Abstract
PURPOSE Emerging evidence revealed that brain-derived neurotrophic factor (BDNF), secreted protein acidic and rich in cysteine (SPARC), fibroblast growth factor 21(FGF-21) and growth differentiation factor 15 (GDF-15) are involved in energy metabolism and body weight regulation. Our study aimed at examining their association with BMI, their alterations after anti-obesity treatments, and their association with 1-year weight loss. METHODS A prospective observational study of 171 participants with overweight and obesity and 46 lean controls was established. All participants received lifestyle educational intervention (LEI) with or without anti-obesity treatments (LEI + bariatric/metabolic surgery, n = 41; LEI + topiramate, n = 46; LEI + liraglutide, n = 31; LEI + orlistat, n = 12; and LEI alone, n = 41). Anthropometric and metabolic parameters, insulin sensitivity, C-reactive protein (CRP), fasting plasma levels of BDNF, SPARC, GDF-15, and FGF-21 were measured at baseline and 1 year. RESULTS Multiple linear regression showed that fasting levels of SPARC, FGF-21, and GDF-15 were significantly associated with baseline BMI after adjustment for age and sex. At 1 year, the average weight loss was 4.8% in the entire cohort with a significant improvement in glycemia, insulin sensitivity, and CRP. Multiple linear regression adjusted for age, sex, baseline BMI, type of treatment, and presence of T2DM revealed that the decrease in log10FGF-21 and log10GDF-15 at 1 year from baseline was significantly associated with a greater percentage of weight loss at 1 year. CONCLUSIONS This study highlights the association of SPARC, FGF-21, and GDF-15 levels with BMI. Decreased circulating levels of GDF-15 and FGF-21 were associated with greater weight loss at 1 year, regardless of the types of anti-obesity modalities.
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Affiliation(s)
- Kusuma Chaiyasoot
- Division of Nutrition, Department of Medicine, Mahidol University, Bangkok, Thailand
| | - Nanta Khumkhana
- Division of Nutrition, Department of Medicine, Mahidol University, Bangkok, Thailand
| | - Wanjan Deekum
- Division of Nutrition, Department of Medicine, Mahidol University, Bangkok, Thailand
| | - Chartchai Chaichana
- Siriraj Center of Research Excellence for Diabetes and Obesity, Mahidol University, Bangkok, Thailand
| | - Voraboot Taweerutchana
- Division of Minimal Invasive Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nicha Srisuworanan
- Division of Minimal Invasive Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Pornpoj Pramyothin
- Division of Nutrition, Department of Medicine, Mahidol University, Bangkok, Thailand.
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Molière S, Jaulin A, Tomasetto CL, Dali-Youcef N. Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease. Int J Mol Sci 2023; 24:10649. [PMID: 37445827 DOI: 10.3390/ijms241310649] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/21/2023] [Accepted: 06/24/2023] [Indexed: 07/15/2023] Open
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes.
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Affiliation(s)
- Sébastien Molière
- Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch, 67400 Illkirch-Graffenstaden, France
- Centre National de la Recherche Scientifique, UMR 7104, 67400 Illkirch-Graffenstaden, France
- Institut National de la Santé et de la Recherche Médicale, U1258, 67400 Illkirch-Graffenstaden, France
- Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- Department of Radiology, Strasbourg University Hospital, Hôpital de Hautepierre, Avenue Molière, 67200 Strasbourg, France
- Breast and Thyroid Imaging Unit, ICANS-Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, France
| | - Amélie Jaulin
- Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch, 67400 Illkirch-Graffenstaden, France
- Centre National de la Recherche Scientifique, UMR 7104, 67400 Illkirch-Graffenstaden, France
- Institut National de la Santé et de la Recherche Médicale, U1258, 67400 Illkirch-Graffenstaden, France
- Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Catherine-Laure Tomasetto
- Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch, 67400 Illkirch-Graffenstaden, France
- Centre National de la Recherche Scientifique, UMR 7104, 67400 Illkirch-Graffenstaden, France
- Institut National de la Santé et de la Recherche Médicale, U1258, 67400 Illkirch-Graffenstaden, France
| | - Nassim Dali-Youcef
- Institut de Génétique et de Biologie Moléculaire et Cellulaire Illkirch, 67400 Illkirch-Graffenstaden, France
- Centre National de la Recherche Scientifique, UMR 7104, 67400 Illkirch-Graffenstaden, France
- Institut National de la Santé et de la Recherche Médicale, U1258, 67400 Illkirch-Graffenstaden, France
- Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- Laboratoire de Biochimie et Biologie Moléculaire, Pôle de Biologie, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 67000 Strasbourg, France
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Valadez LZM, Frigolet ME, Dominguez RM, Pescarus R, Zerrweck C, Boudreau V, Doumouras A, Cookson T, Anvari M. Metabolic and Bariatric Surgery in Diabetes Management. THE DIABETES TEXTBOOK 2023:673-690. [DOI: 10.1007/978-3-031-25519-9_42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022; 55:1609-1626.e7. [PMID: 35963236 PMCID: PMC9474643 DOI: 10.1016/j.immuni.2022.07.007] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 04/06/2022] [Accepted: 07/14/2022] [Indexed: 01/01/2023]
Abstract
The risk of chronic diseases caused by aging is reduced by caloric restriction (CR)-induced immunometabolic adaptation. Here, we found that the matricellular protein, secreted protein acidic and rich in cysteine (SPARC), was inhibited by 2 years of 14% sustained CR in humans and elevated by obesity. SPARC converted anti-inflammatory macrophages into a pro-inflammatory phenotype with induction of interferon-stimulated gene (ISG) expression via the transcription factors IRF3/7. Mechanistically, SPARC-induced ISGs were dependent on toll-like receptor-4 (TLR4)-mediated TBK1, IRF3, IFN-β, and STAT1 signaling without engaging the Myd88 pathway. Metabolically, SPARC dampened mitochondrial respiration, and inhibition of glycolysis abrogated ISG induction by SPARC in macrophages. Furthermore, the N-terminal acidic domain of SPARC was required for ISG induction, while adipocyte-specific deletion of SPARC reduced inflammation and extended health span during aging. Collectively, SPARC, a CR-mimetic adipokine, is an immunometabolic checkpoint of inflammation and interferon response that may be targeted to delay age-related metabolic and functional decline.
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Affiliation(s)
- Seungjin Ryu
- Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
| | - Sviatoslav Sidorov
- Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA
| | - Maxim Artyomov
- Section of Immunology, Washington School of Medicine, St Louis, MO 63110, USA
| | - Akiko Iwasaki
- Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA
| | - Andrew Wang
- Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA
| | - Vishwa Deep Dixit
- Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA; Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06520, USA.
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M1 Polarized Macrophages Persist in Skin of Post-Bariatric Patients after 2 Years. Aesthetic Plast Surg 2022; 46:287-296. [PMID: 34750657 DOI: 10.1007/s00266-021-02649-x] [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: 07/14/2021] [Accepted: 10/23/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Obesity is considered a condition of systemic chronic inflammation. Under this condition, adipose tissue macrophages switch from an M2 (anti-inflammatory) activation pattern to an M1 (proinflammatory) activation pattern. OBJECTIVE The study aimed to verify the profile of skin macrophage activation after bariatric surgery as well as the role of MMP-1 in extracellular tissue remodeling. METHODS This is a prospective, controlled and comparative study with 20 individuals split into two groups according to their skin condition: post-bariatric and eutrophic patients. Histological and morphometric analyses based on hematoxylin-eosin, picrosirius red (collagen), orcein (elastic fiber systems), and alcian blue (mast cells)-stained sections and immunohistochemical analysis (CD68, iNOS, and mannose receptor) for macrophages and metalloproteinase-1 were performed. RESULTS Post-bariatric skin showed an increase in inflammation, angiogenesis, CD68, M1 macrophages (P< 0.001), and mast cells (P< 0.01); a decrease in M2 macrophages (P< 0.01); and a significant decrease in the collagen fiber network (P< 0.001). MMP-1 was increased in the papillary dermis of post-bariatric skin and decreased in the epidermis compared to eutrophic skin (P< 0.05). CONCLUSION This study shows that post-bariatric skin maintains inflammatory characteristics for two years. Mast cells and M1 macrophages maintain and enhance the remodeling of the dermal extracellular matrix initiated during obesity in part due to the presence of MMP-1 in the papillary dermis. EBM LEVEL IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Ren Y, Zhao H, Yin C, Lan X, Wu L, Du X, Griffiths HR, Gao D. Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation. Front Endocrinol (Lausanne) 2022; 13:873699. [PMID: 35909571 PMCID: PMC9329830 DOI: 10.3389/fendo.2022.873699] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 06/17/2022] [Indexed: 11/18/2022] Open
Abstract
Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines - proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.
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Affiliation(s)
- Yakun Ren
- Institute of Molecular and Translational Medicine, Xian Jiaotong University Health Science Center, Xi’an, China
| | - Hao Zhao
- School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Chunyan Yin
- Department of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Xi Lan
- Institute of Molecular and Translational Medicine, Xian Jiaotong University Health Science Center, Xi’an, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Litao Wu
- Institute of Molecular and Translational Medicine, Xian Jiaotong University Health Science Center, Xi’an, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Xiaojuan Du
- Institute of Molecular and Translational Medicine, Xian Jiaotong University Health Science Center, Xi’an, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Helen R. Griffiths
- Swansea University Medical School, Swansea University, Swansea, United Kingdom
| | - Dan Gao
- Institute of Molecular and Translational Medicine, Xian Jiaotong University Health Science Center, Xi’an, China
- Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Center, Xi’an, China
- *Correspondence: Dan Gao,
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Zhu YS, Zhang JN, Mo TT, Jiang C, Ma RC, Chen L. Discoidin domain receptor 2 activation of p38 mitogen-activated protein kinase as an important pathway for osteonectin-regulating osteoblast mineralization. J Orthop Surg Res 2021; 16:711. [PMID: 34876214 PMCID: PMC8650413 DOI: 10.1186/s13018-021-02860-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/24/2021] [Indexed: 11/24/2022] Open
Abstract
Objective The present study aimed to determine the role of the discoidin domain receptor 2 (DDR2) in the osteonectin (ON) regulation of osteoblast mineralization through the activation of p38 mitogen-activated protein kinase (MAPK). Methods Four groups were established: the ON group, the inhibitor group, the Ddr2-small interfering ribonucleic acid (siRNA) group, and the control group. Osteoblasts from the parietal bones of neonatal Sprague–Dawley rats were isolated and cultured. In the ON group, 1 µg/mL ON was added to the osteoblasts. The gene expressions of collagen 1 (Col 1) and Ddr2 were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In the inhibitor group, the osteoblasts were added to WRG-28 (a specific DDR2 inhibitor), and in the Ddr2-siRNA group, the osteoblasts were transfected with Ddr2-siRNA. The gene and protein expressions of DDR2, bone sialoprotein, osteocalcin, osteopontin, and p38 MAPK were determined using RT-qPCR and western blot analysis. Alizarin red staining and transmission electron microscopy were used to detect mineralization. Results The results showed that ON enhanced the osteoblast Col 1 and Ddr2 gene expressions, while the use of a Ddr2-siRNA/DDR2-blocker decreased the OPN, BSP, OCN, and P38 gene and protein expressions and reduced osteoblast cellular activity and mineralized nodules. Conclusion The present study demonstrated that DDR2 activation of p38 MAPK is an important approach to ON-regulating osteoblast mineralization.
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Affiliation(s)
- Yun-Sen Zhu
- Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China
| | - Jiang-Nan Zhang
- Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China
| | - Ting-Ting Mo
- Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China
| | - Chang Jiang
- Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China.
| | - Ru-Chao Ma
- Department of Orthopaedic Surgery, The First People's Hospital of Wenling, Chuan'an Nan Road NO 333, Wenling, 317500, Zhejiang, China
| | - Liang Chen
- Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China
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Ghanemi A, Yoshioka M, St-Amand J. Secreted Protein Acidic and Rich in Cysteine as a Molecular Physiological and Pathological Biomarker. Biomolecules 2021; 11:1689. [PMID: 34827687 PMCID: PMC8615851 DOI: 10.3390/biom11111689] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 11/10/2021] [Accepted: 11/12/2021] [Indexed: 01/25/2023] Open
Abstract
Secreted protein acidic and rich in cysteine (SPARC) is expressed in diverse tissues and plays roles in various biological functions and processes. Increased serum levels of SPARC or its gene overexpression have been reported following numerous physiological and pathological changes including injuries, exercise, regeneration, obesity, cancer, and inflammation. Such expression pattern interrelation between these biological changes and the SPARC expression/secretion points to it as a biomarker. This property could lead to a variety of potential applications ranging from mechanistic studies and animal model validation to the clinical and therapeutic evaluation of both disease prognosis and pharmacological agents.
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Affiliation(s)
- Abdelaziz Ghanemi
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada; (A.G.); (M.Y.)
- Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada
| | - Mayumi Yoshioka
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada; (A.G.); (M.Y.)
| | - Jonny St-Amand
- Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Québec, QC G1V 4G2, Canada; (A.G.); (M.Y.)
- Department of Molecular Medicine, Faculty of Medicine, Laval University, Québec, QC G1V 0A6, Canada
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Caimi G, Hopps E, Montana M, Urso C, Carollo C, Canino B, Lo Presti R. The function of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in several clinical conditions: Results and analysis of our survey. Clin Hemorheol Microcirc 2021; 78:401-416. [PMID: 33814420 DOI: 10.3233/ch-201094] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30-35 Kg/m2 and BMI > 35 Kg/m2); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI > 30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1.
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Affiliation(s)
- Gregorio Caimi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Universitá degli Studi di Palermo, Palermo, Italy
| | - Eugenia Hopps
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Universitá degli Studi di Palermo, Palermo, Italy
| | - Maria Montana
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Universitá degli Studi di Palermo, Palermo, Italy
| | | | - Caterina Carollo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Universitá degli Studi di Palermo, Palermo, Italy
| | - Baldassare Canino
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Universitá degli Studi di Palermo, Palermo, Italy
| | - Rosalia Lo Presti
- Department of Psychology, Educational Science and Human Movement, Universitá degli Studi di Palermo, Palermo, Italy
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18
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Metabolic adaptations after bariatric surgery: adipokines, myokines and hepatokines. Curr Opin Pharmacol 2020; 52:67-74. [PMID: 32688292 DOI: 10.1016/j.coph.2020.06.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/13/2020] [Accepted: 06/15/2020] [Indexed: 12/23/2022]
Abstract
This review addresses the impact of bariatric surgery on the endocrine aspects of white adipose tissue, muscle and the liver. We describe literature supporting the notion that adipokines, myokines and hepatokines likely act in concert and drive many of the long-term metabolic improvements following surgery. Circulating adiponectin is increased while secretion of pro-inflammatory interleukins (1, 6 and 8) decreases, alongside leptin secretion. The metabolic improvements observed in the muscle might relate to reduction of myokines contributing to insulin resistance (including myostatin, brain-derived neurotrophic factor and fibroblast growth factor-21). Subject to exception, hepatokine secretion is generally increased (such as insulin-like growth factor-binding protein 2, adropin and sex hormone-binding globulin). In conclusion, bariatric surgery restores metabolic functions by enhancing the time-dependent secretion of anti-inflammatory, insulin-sensitizing and antilipemic factors. Further research is needed to understand the molecular mechanisms by which these factors may trigger the remission of obesity-related comorbidities following bariatric surgery.
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19
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Matrix Metalloproteinases in Obesity After Gastric Bypass Surgery—an Experimental Study. Indian J Surg 2020. [DOI: 10.1007/s12262-020-02462-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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20
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21
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Sajoux I, Lorenzo PM, Gomez-Arbelaez D, Zulet MA, Abete I, Castro AI, Baltar J, Portillo MP, Tinahones FJ, Martinez JA, Crujeiras AB, Casanueva FF. Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity. Nutrients 2019; 11:nu11102368. [PMID: 31590286 PMCID: PMC6835835 DOI: 10.3390/nu11102368] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 09/03/2019] [Accepted: 09/24/2019] [Indexed: 12/14/2022] Open
Abstract
: The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet.
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Affiliation(s)
- Ignacio Sajoux
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
- Medical Department Pronokal, Protein Supplies SL, Barcelona 08009, Spain.
| | - Paula M Lorenzo
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
| | - Diego Gomez-Arbelaez
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
- Faculty of Health Sciences, University of Santander (UDES), 680003 Bucaramanga, Colombia.
| | - M Angeles Zulet
- Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra (UNAV) and IdiSNA, Navarra Institute for Health Research, 31009 Pamplona, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Itziar Abete
- Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra (UNAV) and IdiSNA, Navarra Institute for Health Research, 31009 Pamplona, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Ana I Castro
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Javier Baltar
- Division of General Surgery, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), 15706 Santiago de Compostela, Spain.
| | - María P Portillo
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, 01005 Vitoria, Spain.
| | - Francisco J Tinahones
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Complejo Hospitalario de Málaga (Virgen de la Victoria), Universidad de Málaga, |29010 Málaga, Spain.
| | - J Alfredo Martinez
- Department of Nutrition, Food Science and Physiology, Centre for Nutrition Research, University of Navarra (UNAV) and IdiSNA, Navarra Institute for Health Research, 31009 Pamplona, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Program for Precision Nutrition, IMDEA, 28049 Madrid, Spain.
| | - Ana B Crujeiras
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
- Laboratory of Epigenomics in Endocrinology and Nutrition, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), 15706 Santiago de Compostela, Spain.
| | - Felipe F Casanueva
- Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.
- CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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Savedoroudi P, Bennike TB, Kastaniegaard K, Talebpour M, Ghassempour A, Stensballe A. Serum proteome changes and accelerated reduction of fat mass after laparoscopic gastric plication in morbidly obese patients. J Proteomics 2019; 203:103373. [PMID: 31054967 DOI: 10.1016/j.jprot.2019.05.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/29/2019] [Accepted: 05/01/2019] [Indexed: 02/06/2023]
Abstract
Laparoscopic Gastric Plication (LGP) is a relatively new bariatric surgical procedure which no part of the stomach is removed. It is not clearly understood how LGP leads to fatty tissue reduction. We aimed to investigate the impact of LGP on serum proteome and understand molecular mechanisms of LGP-induced weight loss post-surgery. A Prospective observational study of 16 obese individuals who underwent LGP was performed. A Label-free quantitative shotgun proteomics approach was used to compare serum proteome of subjects before surgery with serum of the same individuals 1 to 2 months post-surgery (T1) and 4 to 5 months post-surgery (T2). The proteome analysis revealed that 48 proteins were differentially regulated between pre-surgery and T1, and seven proteins between pre-surgery and T2 of which six proteins were shared between the two timepoints. Among differentially regulated proteins, four proteins (SRGN, FETUB, LCP1 and CFP) have not previously been described in the context of BMI/weight loss. Despite few differences following LGP, most regulated serum proteins are in accordance with alternative weight loss procedures. Pathway analysis revealed changes to lipid- and inflammatory pathways, including PPARα/RXRα, LXR/RXR and FXR/RXR activation, especially at T1. At T2, the pathways related to inflammation and immune system are most affected. SIGNIFICANCE: Among the available clinical therapies for morbid obesity, bariatric surgery is considered as the most effective approach to achieve long-term weight loss, alongside a significant improvement in metabolic syndrome. However, very little is known about the underlying mechanism associated with significant weight loss post-surgery. Understanding such mechanisms could lead to development of safer non-surgical weight loss approaches. We here present the first analysis of the impact of LGP on the serum proteome, to bring new insights into the underlying molecular mechanism. Our findings indicate that LGP has a comprehensive systemic effect based on the blood serum proteome profile which might account for accelerated reduction of fat mass after surgery, thus, food restriction is not the only reason for weight loss following this unique surgical approach. As secretory regions of the stomach are preserved in LGP and it is associated with minimal physiological and anatomical changes, the findings are of high importance in the field of bariatric surgery and weight loss.
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Affiliation(s)
- Parisa Savedoroudi
- Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran; Department of Health Science and Technology, Aalborg University, Denmark.
| | - Tue Bjerg Bennike
- Department of Health Science and Technology, Aalborg University, Denmark.
| | | | - Mohammad Talebpour
- Laparoscopic Surgery Ward, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Alireza Ghassempour
- Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
| | - Allan Stensballe
- Department of Health Science and Technology, Aalborg University, Denmark.
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Chen X, Gong L, Li Q, Hu J, Liu X, Wang Y, Bai J, Ran X, Wu J, Ge Q, Li R, Xiao X, Li X, Zhang J, Wang Z. The appropriate remodeling of extracellular matrix is the key molecular signature in subcutaneous adipose tissue following Roux-en-Y gastric bypass. Life Sci 2019; 218:265-273. [DOI: 10.1016/j.lfs.2018.12.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 12/24/2018] [Accepted: 12/29/2018] [Indexed: 12/12/2022]
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Does Bariatric Surgery Improve Obesity Associated Comorbid Conditions. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 960:545-570. [PMID: 28585216 DOI: 10.1007/978-3-319-48382-5_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Obesity is a constantly growing health problem which reduces quality of life and life expectancy. Bariatric surgery for obesity is taken into account when all other conservative treatment modalities have failed. Comparison of the multidisciplinary programs with bariatric surgery regarding to weight loss showed that substantial and durable weight reduction have been achieved only with bariatric surgical treatments. However, the benefits of weight loss following bariatric procedures are still debated regarding the pro-inflammatory and metabolic profile of obesity.
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Frikke-Schmidt H, O'Rourke RW, Lumeng CN, Sandoval DA, Seeley RJ. Does bariatric surgery improve adipose tissue function? Obes Rev 2016; 17:795-809. [PMID: 27272117 PMCID: PMC5328428 DOI: 10.1111/obr.12429] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 03/25/2016] [Accepted: 04/20/2016] [Indexed: 12/19/2022]
Abstract
Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.
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Affiliation(s)
| | - R W O'Rourke
- Department of Surgery, University of Michigan, Ann Arbor, USA
| | - C N Lumeng
- Department of Pediatrics, University of Michigan, Ann Arbor, USA
| | - D A Sandoval
- Department of Surgery, University of Michigan, Ann Arbor, USA
| | - R J Seeley
- Department of Surgery, University of Michigan, Ann Arbor, USA
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Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT. J Clin Lipidol 2016; 10:33-57. [DOI: 10.1016/j.jacl.2015.12.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023]
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Bays HE, Jones PH, Jacobson TA, Cohen DE, Orringer CE, Kothari S, Azagury DE, Morton J, Nguyen NT, Westman EC, Horn DB, Scinta W, Primack C. Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY. J Clin Lipidol 2016; 10:15-32. [DOI: 10.1016/j.jacl.2015.12.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023]
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Bauters D, Scroyen I, Van Hul M, Lijnen HR. Gelatinase A (MMP-2) promotes murine adipogenesis. Biochim Biophys Acta Gen Subj 2015; 1850:1449-56. [PMID: 25869489 DOI: 10.1016/j.bbagen.2015.04.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 03/09/2015] [Accepted: 04/03/2015] [Indexed: 01/25/2023]
Abstract
BACKGROUND Expansion of adipose tissue is dependent on adipogenesis, angiogenesis and extracellular matrix remodeling. A functional role in these processes was suggested for the gelatinase subfamily of the matrix metalloproteinases. Here, we have evaluated a potential role of gelatinase A (MMP-2) in adipogenesis. METHODS Murine embryonic fibroblasts (MEF) were derived from wild-type or MMP-2 deficient mice. Genetic manipulation of Mmp2 (shRNA-knockdown or overexpression) was performed in 3T3-F442A preadipocytes. Cell cultures were subjected to an adipogenic medium. As an in vivo model for de novo adipogenesis, 3T3-F442A preadipocytes with or without knockdown were injected subcutaneously in Nude BALB/c mice kept on high fat diet. RESULTS Mmp2 deficient MEF, as compared to controls, showed significantly impaired differentiation into mature adipocytes, as demonstrated by 90% reduced intracellular lipid content and reduced expression of pro-adipogenic markers. Moreover, selective Mmp2 knockdown in 3T3-F442A preadipocytes resulted in significantly reduced differentiation. In contrast, overexpression of Mmp2 resulted in markedly enhanced differentiation. In de novo formed fat pads resulting from preadipocytes with Mmp2 knockdown expression of aP2, Ppar-γ and adiponectin was significantly lower, and collagen was more preserved. The fat pad weights as well as size and density of adipocytes or blood vessels were, however, not significantly different from controls. CONCLUSION Our data directly support a functional role of MMP-2 in adipogenesis in vitro, and suggest a potential role in in vivo adipogenesis. GENERAL SIGNIFICANCE Selective modulation of MMP-2 levels affects adipogenesis.
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Affiliation(s)
- Dries Bauters
- KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium
| | - Ilse Scroyen
- KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium
| | - Matthias Van Hul
- KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium
| | - H Roger Lijnen
- KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium.
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Rashti F, Gupta E, Ebrahimi S, Shope TR, Koch TR, Gostout CJ. Development of minimally invasive techniques for management of medically-complicated obesity. World J Gastroenterol 2014; 20:13424-13445. [PMID: 25309074 PMCID: PMC4188895 DOI: 10.3748/wjg.v20.i37.13424] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 06/15/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
The field of bariatric surgery has been rapidly growing and evolving over the past several decades. During the period that obesity has become a worldwide epidemic, new interventions have been developed to combat this complex disorder. The development of new laparoscopic and minimally invasive treatments for medically-complicated obesity has made it essential that gastrointestinal physicians obtain a thorough understanding of past developments and possible future directions in bariatrics. New laparoscopic advancements provide patients and practitioners with a variety of options that have an improved safety profile and better efficacy without open, invasive surgery. The mechanisms of weight loss after bariatric surgery are complex and may in part be related to altered release of regulatory peptide hormones from the gut. Endoscopic techniques designed to mimic the effects of bariatric surgery and endolumenal interventions performed entirely through the gastrointestinal tract offer potential advantages. Several of these new techniques have demonstrated promising, preliminary results. We outline herein historical and current trends in the development of bariatric surgery and its transition to safer and more minimally invasive procedures designed to induce weight loss.
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Röhrborn D, Eckel J, Sell H. Shedding of dipeptidyl peptidase 4 is mediated by metalloproteases and up-regulated by hypoxia in human adipocytes and smooth muscle cells. FEBS Lett 2014; 588:3870-7. [PMID: 25217834 DOI: 10.1016/j.febslet.2014.08.029] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 08/13/2014] [Accepted: 08/27/2014] [Indexed: 12/12/2022]
Abstract
Dipeptidyl peptidase 4 is an important drug target for diabetes and a novel adipokine. However, it is unknown how soluble DPP4 (sDPP4) is cleaved from the cell membrane and released into the circulation. We show here that MMP1, MMP2 and MMP14 are involved in DPP4 shedding from human vascular smooth muscle cells (SMC) and MMP9 from adipocytes. Hypoxia increased DPP4 shedding from SMC which is associated with increased mRNA expression of MMP1. Our data suggest that constitutive as well as hypoxia-induced DPP4 shedding occurs due to a complex interplay between different MMPs in cell type-specific manner.
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Affiliation(s)
- Diana Röhrborn
- Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany
| | - Jürgen Eckel
- Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany
| | - Henrike Sell
- Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
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Murphy-Ullrich JE, Sage EH. Revisiting the matricellular concept. Matrix Biol 2014; 37:1-14. [PMID: 25064829 PMCID: PMC4379989 DOI: 10.1016/j.matbio.2014.07.005] [Citation(s) in RCA: 299] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Revised: 07/07/2014] [Accepted: 07/08/2014] [Indexed: 12/16/2022]
Abstract
The concept of a matricellular protein was first proposed by Paul Bornstein in the mid-1990s to account for the non-lethal phenotypes of mice with inactivated genes encoding thrombospondin-1, tenascin-C, or SPARC. It was also recognized that these extracellular matrix proteins were primarily counter or de-adhesive. This review reappraises the matricellular concept after nearly two decades of continuous investigation. The expanded matricellular family as well as the diverse and often unexpected functions, cellular location, and interacting partners/receptors of matricellular proteins are considered. Development of therapeutic strategies that target matricellular proteins are discussed in the context of pathology and regenerative medicine.
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Affiliation(s)
- Joanne E Murphy-Ullrich
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, United States.
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