Exp Clin Endocrinol Diabetes 2020; 128(05): 290-296
DOI: 10.1055/a-0725-7897
Article
© Georg Thieme Verlag KG Stuttgart · New York

Angiopoietin-like 8 Improves Insulin Resistance and Attenuates Adipose Tissue Inflammation in Diet-Induced Obese Mice

Deng Luo
1   Department of Endocrinology, Renmin Hospital, Wuhan University, Wuhan, 430060, China
,
Xiaolin Chen
1   Department of Endocrinology, Renmin Hospital, Wuhan University, Wuhan, 430060, China
,
Wenqiang Yang
2   Department of Clinical Laboratory, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, China
,
Wenzhuo Ran
2   Department of Clinical Laboratory, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, China
,
Zhongyuan Wen
1   Department of Endocrinology, Renmin Hospital, Wuhan University, Wuhan, 430060, China
› Author Affiliations
Funding: This study was funded by grants from the application foundation planning project of Wuhan Science and Technology Bureau (2015061701011619); Independent Research Project of Wuhan University of China, No.2042017kf0084; Natural Science Foundation of Hubei Province (No. 2018CFB230).
Further Information

Publication History

received 21 March 2018
revised  24 August 2018

accepted 30 August 2018

Publication Date:
26 September 2018 (online)

Abstract

Angiopoietin-like 8 (ANGPTL8) is closely linked to obesity-associated metabolic diseases and insulin resistance. The aim of the current study was to investigate the ability of ANGPTL8 to reverse insulin resistance in obese mice. The administration of ANGPTL8 reduced weight gain and improved glucose tolerance in mice with diet-induced obesity. In addition, ANGPTL8 administration modified macrophage infiltration, reduced monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β(IL-1β) levels, and increased adiponectin gene expression in inguinal white adipose tissue (iWAT). Moreover, the exposure of a cultured peritoneal macrophage line to ANGPTL8 reduced the mRNA expression of M1 macrophage markers (TNF-α and IL-1β) upon stimulation with lipopolysaccharides in a dose-dependent manner. By contrast, when incubated with IL-4, exposure of macrophages to ANGPTL8 increased the mRNA expression of M2 macrophage markers (Arg1 and Chi3l3) in a dose-dependent manner. Collectively, the results of the present study demonstrated that treatment with ANGPTL8 can attenuate adipose tissue inflammation through regulation of macrophage polarization, and thus, it could be useful for improving insulin resistance.

Supplementary Material

 
  • References

  • 1 Ye L, Liang S, Guo C. et al. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance. Life Sci 2016; 166: 82-91
  • 2 Abu-Farha M, AI-Khairi I, Cherian P. et al. Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D. Lipids Health Dis 2016; 15: 181
  • 3 Ejarque M, Borlaug M, Vilarrasa N. et al. Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery. Transl Res 2017; 184: 35-44.e4
  • 4 Qu Q, Zhao D, Zhang F. et al. Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome. J Int Med Res 2017; 45: 193-202
  • 5 Yi P, Park JS, Melton DA. Retraction Notice to: Betatrophin: A hormone that controls pancreatic beta cell proliferation. Cell 2017; 168: 326
  • 6 Rong Guo X, Li Wang X, Chen Y. et al. ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3beta or Akt-FoxO1 pathway in HepG2 cells. Exp Cell Res 2016; 345: 158-167
  • 7 Liu D, Qu H, Wang H. et al. Relationship between serum betatrophin levels and the first-phase of glucose-stimulated insulin secretion. Obes Res Clin Pract 2018; 12 1S1 9-15
  • 8 Gómez-Ambrosi J, Pascual-Corrales E, Catalán V. et al. Altered Concentrations in Dyslipidemia Evidence a Role for ANGPTL8/Betatrophin in Lipid Metabolism in Humans. J Clin Endocrinol Metab 2016; 101: 3803-3811
  • 9 Tuhan H, Abaci A, Anik A. et al. Circulating betatrophin concentration is negatively correlated with insulin resistance in obese children and adolescents. Diabetes Res Clin Pract 2016; 114: 37-42
  • 10 Maurer L, Brachs S, Decker AM. et al. Weight loss partially restores glucose-driven betatrophin response in humans. J Clin Endocrinol Metab 2016; 101: 4014-4020
  • 11 Guo K, Yu H, Lu J. et al. Decreased serum betatrophin levels correlate with improved fasting plasma glucose and insulin secretion capacity after Roux-en-Y gastric bypass in obese Chinese patients with type 2 diabetes: A 1-year follow-up. Surg Obes Relat Dis 2016; 12: 1343-1348
  • 12 Wang Y, Quagliarini F, Gusarova V. et al. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci USA 2013; 110: 16109-16114
  • 13 Fu Z, Berhane F, Fite A. et al. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep 2014; 4: 5013
  • 14 Winer DA, Winer S, Chng MH. et al. B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell Mol Life Sci 2014; 71: 1033-1043
  • 15 Chen X, Lu P, He W. et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab 2015; 100: E96-E100
  • 16 Quagliarini F, Wang Y, Kozlitina J. et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci USA 2012; 109: 19751-19756
  • 17 Knudsen SH, Pedersen BK. Targeting inflammation through a physical active lifestyle and pharmaceuticals for the treatment of Type 2 Diabetes. Curr Diab Rep 2015; 15: 82
  • 18 van Diepen JA, Berbée JF, Havekes LM. et al. Interactions between inflammation and lipid metabolism: Relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis. Atherosclerosis 2013; 228: 306-315
  • 19 Kanda H, Tateya S, Tamori Y. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006; 116: 1494-1505
  • 20 Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 2003; 100: 7265-7270
  • 21 Kadowali T, Yamauchi T, Kubota N. et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784-1792
  • 22 Awazawa M, Ueki K, Inabe K. et al. Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway. Cell Metab 2011; 13: 401-412
  • 23 Subramanisn S, Pallati PK, Sharma P. et al. TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population. J Transl Med 2017; 15: 85
  • 24 Suzuki T, Gao J, Ishigaki Y. et al. ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity. Cell Rep 2017; 18: 2045-2057