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

Caio Yogi Yonamine1,*,

Silvania Silva Teixeira1,

Raquel Saldanha Campello1,

Frederico Gerlinger-Romero1,

Carlos Flores Rodrigues Jr.1,

Lucas Guimarães-Ferreira2,

Ubiratan Fabres Machado1 and

Maria Tereza Nunes1

 

DOI: 10.1111/apha.12336

Abstract

Aim

Investigate, in healthy sedentary rats, the potential mechanisms involved on the effects of beta hydroxy beta methylbutyrate (HMB) supplementation upon the glycemic 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−1BW) 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: 1) higher ratio between the area under the curve (AUC) of insulinemia and glycemia during glucose tolerance test; 2) impairment of insulin sensitivity on liver and soleus skeletal muscle after insulin overload; 3) reduction of glucose transporter 4 (GLUT 4) total and plasma membrane content on soleus; 4) increased hormone sensitive lipase (HSL) mRNA and protein expression on white adipose tissue and plasma non-esterified fatty acids (NEFA) levels and 5) 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.