Abstract
Purpose Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. Methods Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. Results Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. Conclusion Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.
Highlights
Over the past decades, the prevalence of obesity and diabetes increased rapidly, causing great social burden around the world [1,2,3]
Elevated fasting blood glucose (FBG) in DIO mice was not affected by Neuromedin U (NMU) (Supplementary Figure 1(c)). ese results suggest that NMU could improve glucose tolerance when energy intake and body weight remain steady
We proved that peripherally administered NMU
Summary
The prevalence of obesity and diabetes increased rapidly, causing great social burden around the world [1,2,3]. As a major risk factor of type 2 diabetes mellitus, obesity is associated with the imbalance between energy intake and energy expenditure and is characterized with expanded adipose tissue (AT) mass in the body [4, 5]. BAT consists of multilocular adipocytes with increased numbers of mitochondria that express uncoupling protein 1 (UCP1). Beige adipocytes express UCP1 protein and exhibit thermogenic capacity at a comparable level to BAT [4, 6, 7]. WAT is excessively accumulated in the body, causing local immune abnormalities, tissue fibrosis, and AT secretome changes, which drive peripheral insulin resistance and contribute to the pathogenesis of type 2 diabetes mellitus [4]. Effective ways to promote WAT beiging are still under investigation
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