Premium
The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation
Author(s) -
AguileraMéndez Asdrúbal,
FernándezMejía Cristina
Publication year - 2012
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1034
Subject(s) - biotin , ampk , acetyl coa carboxylase , endocrinology , medicine , sterol regulatory element binding protein , lipogenesis , pyruvate carboxylase , triglyceride , fatty acid synthase , chemistry , biotin deficiency , amp activated protein kinase , phosphorylation , protein kinase a , biochemistry , biology , lipid metabolism , enzyme , cholesterol , sterol
In addition to its role as a carboxylase cofactor, biotin modifies gene expression and has manifold effects on systemic processes. Several studies have shown that biotin supplementation reduces hypertriglyceridemia. We have previously reported that this effect is related to decreased expression of lipogenic genes. In the present work, we analyzed signaling pathways and posttranscriptional mechanisms involved in the hypotriglyceridemic effects of biotin. Male BALB/cAnN Hsd mice were fed a control or a biotin‐supplemented diet (1.76 or 97.7 mg of free biotin/kg diet, respectively for 8 weeks after weaning. The abundance of mature sterol regulatory element‐binding protein (SREBP‐1c), fatty‐acid synthase (FAS), total acetyl‐CoA carboxylase‐1 (ACC‐1) and its phosphorylated form, and AMP‐activated protein kinase (AMPK) were evaluated in the liver. We also determined the serum triglyceride concentrations and the hepatic levels of triglycerides and cyclic GMP (cGMP). Compared to the control group, biotin‐supplemented mice had lower serum and hepatic triglyceride concentrations. Biotin supplementation increased the levels of cGMP and the phosphorylated forms of AMPK and ACC‐1 and decreased the abundance of the mature form of SREBP‐1c and FAS. These data provide evidence that the mechanisms by which biotin supplementation reduces lipogenesis involve increased cGMP content and AMPK activation. In turn, these changes lead to augmented ACC‐1 phosphorylation and decreased expression of both the mature form of SREBP‐1c and FAS. Our results demonstrate for the first time that AMPK is involved in the effects of biotin supplementation and offer new insights into the mechanisms of biotin‐mediated hypotriglyceridemic effects.