Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation

Abstract

BackgroundPalmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes.MethodsFor this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from mice treated with 16:1n7 (300 mg/kg/day) or oleic acid (18:1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes.ResultsTreatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p)Thr172AMPKα, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16:1n7, was prevented by pharmacological inhibition of AMPK with compound C.ConclusionsIn conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation.

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

“…For example, Yang et al [49] showed that palmitoleic acid induces satiety in mice, while studies with obese high-fat diet fed mice have shown that daily administration of palmitoleic acid (300 mg kg −1 ) for 10 d increased whole body insulin sensitivity [4,51] and enhanced glucose uptake into adipose tissue by modulation of GLUT-4 content and AMPK phosphorylation. [5] Palmitoleic acid also increased expression of adipose triglyceride lipase and hormone-sensitive lipase (HSL) [24] (Figure 2). This higher expression and activity of Figure 1) reportedly increases insulin secretion by the pancreas, improves insulin sensitivity of the liver and skeletal muscle, reduces inflammation, and promotes numerous beneficial metabolic effects in the liver and cardiovascular system.…”

“…[26] It is important to mention that besides being rich in palmitoleic acid (19%), macadamia oil has a high percentage of oleic acid (56%). [26] However, most of the animal studies presented here [4,5,24,51] compared the treatment of palmitoleic acid to that of oleic acid (e.g., at 300 mg kg −1 ), showing a higher oxidative, lipid lowering, and insulin sensitization with palmitoleic acid.…”

“…Adipose lipolysis, adipose lipase, and hormone sensitive lipase; effects required PPARα [5] 3T3-L1 cells Glucose uptake, glucose oxidation and GLUT4 mRNA levels, DNL Epididymal AT from mice fed palmitoleic acid (300 mg kg −1 d −1 ) for 10 d Basal and insulin-stimulated glucose uptake [4] WT versus PPARα KO mice, on HFD, fed palmitoleic acid (300 mg kg…”

“…[1,2] Palmitoleic acid has been described as produced and released by adipocytes and acting as a lipokine modulating several metabolic processes in other tissues. [3] For example, several studies observed that palmitoleic acid enhanced whole body glucose disposal in rodents, [3][4][5] attenuated hepatic steatosis in high-fatfed and diabetic mice, [3,6] protected pancreatic β cells from death induced by palmitic acid, [7][8][9] and improved the circulating lipid profile in mice [3] and humans. [10] Furthermore, palmitoleic acid supplementation was seen to reduce liver inflammation in mice with nonalcoholic fatty liver disease (NAFLD), [4,11] and to slow the progression of atherosclerosis in obese mice.…”

Fatty Acid β-Oxidation Plays a Key Role in Regulating <i>cis</i>-Palmitoleic Acid Levels in the Liver

“…7) Subsequent studies performed on cultured cells, animals, and humans have suggested that 16:1n-7 enhances whole-body glucose disposal, suppresses hepatic steatosis, reduces stearoyl-CoA desaturase (SCD) 1, and modulates the metabolism of triacylglycerols (TAG) and glucose in white adipose tissue. [6][7][8][9] These findings generated expectations on the physiological significance of 16:1n-7 for metabolic homeostasis in humans. However, several lines of evidence from studies performed on human subjects have suggested contradictory outcomes; namely, circulating levels of 16:1n-7 are not necessarily beneficial for human health.…”