Treatment with the TGF-b superfamily cytokine MIC-1/GDF15 reduces the adiposity and corrects the metabolic dysfunction of mice with diet-induced obesity
| Autor: | Helene Lebhar, Hong Ping Zhang, Samuel N. Breit, Vicky Wang-Wei Tsai, Amanda Sainsbury, David Brown, Christopher P. Marquis, Ka Ki Michelle Lee-Ng, Rakesh Manandhar, Yasmin Husaini |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Growth Differentiation Factor 15 Endocrinology Diabetes and Metabolism medicine.medical_treatment Medicine (miscellaneous) Diet High-Fat Eating Mice 03 medical and health sciences Insulin resistance Internal medicine Animals Medicine Obesity Adiposity Nutrition and Dietetics Adiponectin business.industry Insulin Leptin Body Weight medicine.disease Recombinant Proteins Mice Inbred C57BL 030104 developmental biology Cytokine Endocrinology Immunology GDF15 Energy Metabolism business Thermogenesis |
| Zdroj: | International Journal of Obesity. 42:561-571 |
| ISSN: | 1476-5497 0307-0565 |
| DOI: | 10.1038/ijo.2017.258 |
| Popis: | To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers. MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15 reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed mice lost fat mass alone. This reduction in body weight and adiposity was due largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also displayed increased energy expenditure that may be due to increased thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating level of adiponectin and lower tissue expression, and circulating levels of leptin and inflammatory mediators associated with insulin resistance. Peripheral insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high-fat-fed and chow-fed mice compared to that of their vehicle-treated control mice. MIC-1/GDF15 is highly effective in reducing adiposity and correcting the metabolic dysfunction of mice with high-fat fed. These studies suggest that MIC-1/GDF15 may be a candidate anti-obesity therapeutic. |
| Databáze: | OpenAIRE |
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