Beta hydroxy beta methylbutyrate supplementation impairs peripheral insulin sensitivity in healthy sedentary Wistar rats

Acta Physiol (Oxf). 2014 Sep;212(1):62-74. doi: 10.1111/apha.12336. Epub 2014 Jul 12.

Abstract

Aim: Investigate, in healthy sedentary rats, the potential mechanisms involved on the effects of beta hydroxy beta methylbutyrate (HMB) supplementation upon the glycaemic homeostasis, by evaluating the insulin sensitivity in liver, skeletal muscle, and white adipose tissue.

Methods: Rats were supplemented with either beta hydroxy beta methylbutyrate (320 mg kg(-1) BW) or saline by gavage for 4 weeks. After the experimental period, the animals were subjected to the glucose tolerance test (GTT) and plasma non-esterified fatty acids (NEFA) concentration measurements. The soleus skeletal muscle, liver and white adipose tissue were removed for molecular (western blotting and RT-PCR) and histological analysis.

Results: The beta hydroxy beta methylbutyrate supplemented rats presented: (i) higher ratio between the area under the curve (AUC) of insulinaemia and glycaemia during glucose tolerance test; (ii) impairment of insulin sensitivity on liver and soleus skeletal muscle after insulin overload; (iii) reduction of glucose transporter 4 (GLUT 4) total and plasma membrane content on soleus; (iv) increased hormone-sensitive lipase (HSL) mRNA and protein expression on white adipose tissue and plasma NEFA levels and (v) reduction of fibre cross-sectional area of soleus muscle.

Conclusion: The data altogether indicate that beta hydroxy beta methylbutyrate supplementation impairs insulin sensitivity in healthy sedentary rats, which, in the long-term, could lead to an increased risk of developing type 2 diabetes.

Keywords: beta hydroxy beta methylbutyrate; glucose transporter 4; glycemic homeostasis; growth hormone; insulin resistance; non-esterified fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Animals
  • Blotting, Western
  • Dietary Supplements / toxicity*
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / metabolism
  • Insulin Resistance / physiology*
  • Liver / drug effects
  • Male
  • Muscle, Skeletal / drug effects*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Valerates / toxicity*

Substances

  • Glucose Transporter Type 4
  • Valerates
  • beta-hydroxyisovaleric acid