Spinophilin-deficient mice are protected from diet-induced obesity and insulin resistance

Yong Zhang, Lili Song, Huansheng Dong, Do Sung Kim, Zhen Sun, Heather Boger, Qin Wang, Hongjun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Browning of white adipose tissue (WAT) has been shown to reduce obesity and obesity-related complications, suggesting that factors that promote WAT browning may have applications in the development of therapeutic strategies for treating obesity. Here, we show that ablation of spinophilin (SPL), a ubiquitously expressed, multidomain scaffolding protein, increases metabolism and improves energy balance. Male and female SPL knockout (KO) and wild-type (WT) littermate controls were fed a chow diet or a high-fat diet (HFD). Body weight, hepatic steatosis, glucose and insulin tolerance, physical activity, and expression of browning genes in adipose tissues were measured and compared. Male SPL knockout (KO) mice fed a chow diet were significantly leaner, had lower body weights, and exhibited better glucose tolerance and insulin sensitivity than wild-type (WT) littermate controls. When fed an HFD, SPL KO mice were protected from increased body fat, weight gain, hepatic steatosis, hyperinsulinemia, and insulin resistance. Physical activity of SPL KO mice was markedly increased compared with WT controls. Furthermore, expression of the brown adipocyte marker, uncoupling protein-1 (UCP-1), and the mitochondrial activity markers, cd137 and c-idea, were significantly increased in visceral WAT (vWAT) of SPL KO mice, suggesting that SPL knockout protected the mice from HFD-induced obesity and its metabolic complications, at least in part, by promoting the browning of white adipocytes in vWAT. Our data identify a critical role of SPL in regulating glucose homeostasis, obesity, and adipocyte browning. These results suggest SPL may serve as a drug target for obesity and diabetes.

Original languageEnglish (US)
Pages (from-to)E354-E362
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume319
Issue number2
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • Activity
  • Browning
  • Insulin sensitivity
  • Obesity
  • Spinophilin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Spinophilin-deficient mice are protected from diet-induced obesity and insulin resistance'. Together they form a unique fingerprint.

Cite this