title: Effects of Biotin Supplementation in the Diet on Adipose Tissue cGMP Concentrations, AMPK Activation, Lipolysis, and Serum-Free Fatty Acid Levels.
abstract: Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 μmol/mL; supplemented: 0.33±0.08 μmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.
authors.affiliation: Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Instituto Nacional de Pediatría, Mexico City, Mexico .
authors.forename: Daniel
authors.initials: D
authors.lastname: Boone-Villa
authors.affiliation: Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Instituto Nacional de Pediatría, Mexico City, Mexico .
authors.forename: Asdrubal
authors.initials: A
authors.lastname: Aguilera-Méndez
authors.affiliation: Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Instituto Nacional de Pediatría, Mexico City, Mexico .
authors.forename: Adriana
authors.initials: A
authors.lastname: Miranda-Cervantes
authors.affiliation: Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México , Instituto Nacional de Pediatría, Mexico City, Mexico .
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernandez-Mejia
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000032:analysis / Q000378:metabolism; D000273:Adipose Tissue / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001710:Biotin / Q000008:administration & dosage*; D006152:Cyclic GMP / Q000032:analysis*; D019587:Dietary Supplements; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation
chemical_list: D005230:Fatty Acids, Nonesterified; D001710:Biotin; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D006152:Cyclic GMP
keywords: AMPK; adipose tissue; biotin; cGMP; free fatty acids; hypertriglyceridemia; lipolysis