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Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue

Philip M M Ruppert1, Charlotte C J R Michielsen1, Eric J Hazebroek2

  • 1Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.

Molecular Metabolism
|June 7, 2020
PubMed
Abstract

Insights

Fasting increases angiopoietin-like 4 (ANGPTL4) in human fat tissue, which inhibits lipoprotein lipase (LPL) activity. This study confirms mouse findings in humans, showing fasting reduces LPL activity by increasing ANGPTL4.

Area of Science:

  • Metabolism and Endocrinology
  • Adipose Tissue Biology
  • Lipid Metabolism

Background:

  • Lipoprotein lipase (LPL) activity in adipose tissue is crucial for triglyceride clearance.
  • Fasting in mice leads to decreased LPL activity, mediated by the inhibitor angiopoietin-like 4 (ANGPTL4).
  • Human studies are needed to validate the role of ANGPTL4 in fasting-induced changes in LPL activity.

Purpose of the Study:

  • To investigate the effect of prolonged fasting on ANGPTL4 and LPL gene and protein expression in human subcutaneous adipose tissue.
  • To determine if the mouse model findings regarding ANGPTL4 and LPL regulation during fasting translate to humans.

Main Methods:

  • Twenty-three volunteers underwent a prolonged fast (24 hours) after a standardized meal.
  • Subcutaneous adipose tissue biopsies and blood samples were collected before and after the fasting period.
  • Gene and protein expression of ANGPTL4 and LPL, as well as plasma hormone and metabolite levels, were analyzed.

Main Results:

  • Fasting significantly decreased adipose tissue LPL activity by 60% and increased ANGPTL4 mRNA by 90%.
  • ANGPTL4 protein levels in adipose tissue and plasma increased significantly with fasting.
  • Insulin levels decreased, while cortisol and fatty acids increased, correlating with ANGPTL4 regulation in adipocytes.

Conclusions:

  • Fasting increases ANGPTL4 in human adipose tissue, leading to reduced LPL activity.
  • Hormonal changes (decreased insulin, increased cortisol) and elevated free fatty acids contribute to fasting-induced ANGPTL4 upregulation.
  • This study validates the role of ANGPTL4 as a key regulator of LPL activity during fasting in humans.
Keywords:
Adipose tissueFatty acidsInsulinLipoprotein lipaseTriglycerides

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