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Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized

Gijs H Goossens1, Chantalle C M Moors, Nynke J van der Zijl

  • 1Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands. G.Goossens@maastrichtuniversity.nl

Plos One
|July 7, 2012
PubMed
Abstract

Insights

Valsartan treatment reduced adipocyte size and inflammation markers in individuals with impaired glucose metabolism. This suggests targeting the renin-angiotensin system may improve adipose tissue function and reduce type 2 diabetes risk.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome
  • Cardiovascular Disease Research

Background:

  • Renin-angiotensin system (RAS) blockade is known to reduce type 2 diabetes mellitus incidence.
  • Rodent studies indicate RAS blockade improves adipose tissue (AT) function and glucose homeostasis.
  • Human data on long-term RAS blockade effects on AT function are limited.

Purpose of the Study:

  • To investigate the effects of 26-week valsartan treatment on adipose tissue function in humans with impaired glucose metabolism (IGM).
  • To assess changes in adipocyte size, gene expression, and blood flow in response to valsartan.

Main Methods:

  • A 26-week randomized, double-blind, placebo-controlled study involving 38 subjects with IGM.
  • Treatment with valsartan (320 mg/d) or placebo.
  • Analysis of abdominal subcutaneous AT biopsies for adipocyte size and gene/protein expression (angiogenesis, adipogenesis, inflammation markers).
  • Evaluation of AT blood flow (ATBF), systemic inflammation, and insulin sensitivity.

Main Results:

  • Valsartan significantly reduced adipocyte size, increasing the proportion of small adipocytes (P<0.001).
  • Fasting and postprandial ATBF increased significantly with valsartan treatment (P=0.043, P=0.049).
  • Gene expression of angiogenesis, adipogenesis, and macrophage infiltration markers in AT decreased with valsartan compared to placebo.
  • Decreased adipocyte size correlated with improved insulin sensitivity and reduced AT macrophage infiltration markers.

Conclusions:

  • 26-week valsartan treatment reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, while increasing ATBF in IGM subjects.
  • The reduction in adipocyte size was associated with decreased expression of AT macrophage infiltration markers.
  • Targeting the RAS with valsartan may improve AT function, potentially reducing the risk of cardiovascular disease and type 2 diabetes.

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