Details

Autor(en) / Beteiligte

• Zhang, Lu
• Shannon, Chris E
• Bakewell, Terry M
• Abdul-Ghani, Muhammad A
• Fourcaudot, Marcel
• Norton, Luke

Titel

Regulation of ANGPTL8 in liver and adipose tissue by nutritional and hormonal signals and its effect on glucose homeostasis in mice

Ist Teil von

• American journal of physiology: endocrinology and metabolism, 2020-05, Vol.318 (5), p.E613-E624

Ort / Verlag

United States: American Physiological Society

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The angiopoietin-like protein (ANGPTL) family represents a promising therapeutic target for dyslipidemia, which is a feature of obesity and type 2 diabetes (T2DM). The aim of the present study was to determine the metabolic role of ANGPTL8 and to investigate its nutritional, hormonal, and molecular regulation in key metabolic tissues. The regulation of gene expression by insulin and glucose was quantified using a combination of in vivo insulin clamp experiments in mice and in vitro experiments in primary and cultured hepatocytes and adipocytes. The role of AMPK signaling was examined, and the transcriptional control of was determined using bioinformatic and luciferase reporter approaches. The metabolism of knockout mice (ANGPTL8 ) was examined following chow and high-fat diets (HFD). Insulin acutely increased expression in liver and adipose tissue, which involved the CCAAT/enhancer-binding protein (C/EBPβ) transcription factor. In insulin clamp experiments, glucose further enhanced expression in the presence of insulin in adipose tissue. The activation of AMPK signaling antagonized the effect of insulin on expression in hepatocytes and adipocytes. The ANGPTL8 mice had improved glucose tolerance and displayed reduced fed and fasted plasma triglycerides. However, there was no change in body weight or steatosis in ANGPTL8 mice after the HFD. These data show that ANGPTL8 plays important metabolic roles in mice that extend beyond triglyceride metabolism. The finding that insulin, glucose, and AMPK signaling regulate expression may provide important clues about the distinct function of ANGPTL8 in these tissues.