Palmitoleic acid reduces intramuscular lipid and restores insulin sensitivity in obese sheep

Abstract

Obese sheep were used to assess the effects of palmitoleic (C16:1 cis-9) acid infusion on lipogenesis and circulating insulin levels. Infusion of 10 mg/kg body weight (BW)/day C16:1 intravenously in obese sheep reduced ( P<0.01) weight gain by 77%. Serum palmitoleic levels increased ( P<0.05) in a linear manner with increasing levels of C16:1 infusion. Cis-11 vaccenic (C18:1 cis-11) acid, a known elongation product of palmitoleic acid, was also elevated ( P<0.05) in serum after 14 days and 21 days of infusion. Plasma insulin levels were lower ( P<0.05) (10 mg/kg BW/day C16:1) than controls (0 mg/kg BW/day C16:1) at 14 days and 28 days of infusion. Infusion of C16:1 resulted in linear increases in tissue concentrations of palmitoleic, cis-11 vaccenic, eicosapentaenoic, and docosapentaenoic acids in a dose-dependent manner. Total lipid content of the semitendinosus (ST) muscle and mesenteric adipose tissue was reduced ( P<0.01) in both 5 mg/kg and 10 mg/kg BW C16:1 dose levels. Total lipid content and mean adipocyte size in the longissimus muscle was reduced ( P<0.05) in the 10 mg/kg BW C16:1 dose level only, whereas total lipid content and adipocyte size of the subcutaneous adipose tissue was not altered. Total lipid content of the liver was also unchanged with C16:1 infusion. Palmitoleic acid infusion upregulated ( P<0.05) acetyl-CoA carboxylase ( ACC), fatty acid elongase-6 ( ELOVL6), and Protein kinase, AMP-activated, alpha 1 catalytic subunit, transcript variant 1 ( AMPK) mRNA expressions in liver, subcutaneous adipose, and ST muscle compared to the controls. However, mRNA expression of glucose transporter type 4 ( GLUT4) and carnitine palmitoyltransferase 1b ( CPT1B) differed between tissues. In the subcutaneous adipose and liver, C16:1 infusion upregulated ( P<0.05) GLUT4 and CPT1B, whereas these genes were downregulated ( P<0.05) in ST muscle with C16:1 infusion. These results show that C16:1 infusion for 28 days reduced weight gain, intramuscular adipocyte size and total lipid content, and circulating insulin levels. These changes appear to be mediated through alterations in expression of genes regulating glucose uptake and fatty acid oxidation specifically in the muscles.