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.

The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease

“…However, palmitoleate is relatively more abundant in adipose tissue than it is in serum. In animals, infusion of cis-palmitoleate increases the content of cis-palmitoleate in subcutaneous and mesenteric adipose tissue, longissimus and semitendinosus muscles, and the liver (59). This means that increasing circulating palmitoleate influences tissue abundance.…”

Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?

“…Insulin resistance, glucose uptake, liver inflammation ( IL-1β); all independent of PPARα [83] Obese sheep, iv infusion of palmitoleic acid (10 mg kg −1 d −1 ), 28 d Weight gain, plasma cis-vaccenic acid, insulin, total lipid content (ST muscle, MAT), mRNA for ACC, ELOVL6, and AMPK in liver, sub-AT, and ST muscle, mRNA for GLUT4 and CPT1B (sub-AT, liver) [15] Primary BMDM from HFD mice, palmitic and/or palmitoleic acids 750 μM (6 h) NO, cytokine secretion, mRNA for CXCL1, IL-6, TNF, NOS2, mRNA MCP-1, TGFb1, IL-10, IκBα degradation and NFκB translocation; required AMPK [51] Liver of mice on HFD, fed palmitoleic acid (300 mg kg…”

“…[82] Similar to in vitro studies, intravenous palmitoleic acid infusion (10 mg kg −1 body weight d −1 ) upregulated AMPK expression in liver, subcutaneous adipose tissue, and muscle of obese sheep. [83] In addition, palmitoleic acid supplementation (300 mg kg −1 d −1 ) increased the phosphorylation of AMPK in liver of obese mice, [51] an effect that depends on the activation of the pro-oxidative transcription factor, PPARα (Table 5). …”

Flaxseed Oil or n‐7 Fatty Acid‐Enhanced Fish Oil Supplementation Alters Fatty Acid Composition, Plasma Insulin and Serum Ceramide Concentrations, and Gene Expression in Lambs

“…Our supplemental oil diets contained 4–5% supplemental oil (Table ) and are, therefore, below this threshold level. Previous studies in our laboratory used intravenous administration of the POA to avoid biohydrogenation (Duckett et al, ; Long et al, ), a normal process where dietary monounsaturated fatty acids (MUFA) and PUFA are hydrogenated to saturated fatty acids (SFA) to reduce toxicity of dietary lipids in ruminant animals like sheep. Based on the published biohydrogenation rates (78%, Sackmann et al, ; 84%, Duckett and Gillis, ; 87%, Atkinson et al, ) and digestibility values (78%, Glasser et al, ; 90%, Sklan et al, ; 84–89%, Atkinson et al, ), we estimate that the level of palmitoleic acid or ALA reaching the small intestine without biohydrogenation would be about 64–111 mg/kg BW.…”

“…Palmitoleic acid inhibits lipogenesis in bovine primary adipocyte cultures (Burns et al, , ). Intravenous infusion of palmitoleic acid (0–10 mg/kg body weight [BW]) to obese sheep reduces feed intake, BW gain, and insulin resistance in a dose‐dependent manner with higher dose levels resulting in a greater reduction (Duckett et al, ; Long et al, ). However, alterations in body composition during this short‐term study (28 days) were not observed, which may be related to the obese state (40% body fat) attained by mature lambs.…”