Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes

Abstract

BackgroundStudies have demonstrated the beneficial effect of palmitoleic acid (C16:1 n-7) on reducing muscle insulin resistance and preventing beta-cell apoptosis. However, the effect of palmitoleic acid on diabetes remains to be elucidated. The aim of this study was to examine the antidiabetic effect of palmitoleic acid in KK-Ay mice, a spontaneous model for studies of obese type 2 diabetes with low insulin sensitivity.MethodsKK-Ay mice were orally administered vehicle, 300 mg/kg of palmitoleic acid, or 300 mg/kg of palmitic acid (C16:0) on a daily basis for 4 weeks.ResultsPalmitoleic acid reduced body weight increase, ameliorated the development of hyperglycemia and hypertriglyceridemia, and improved insulin sensitivity. In addition, hepatic characteristics were significantly affected, as weight of the liver and hepatic triglyceride levels were lower in the palmitoleic acid group when compared to the control (vehicle and palmitic acid groups). Oil red O staining clearly indicated reduced hepatic lipid accumulation in response to palmitoleic acid. Furthermore, palmitoleic acid down-regulated mRNA expressions of proinflammatory adipocytokine genes (TNFα and resistin) in white adipose tissue and lipogenic genes (SREBP-1, FAS, and SCD-1) in liver.ConclusionsThese results suggest that palmitoleic acid improves hyperglycemia and hypertriglyceridemia by increasing insulin sensitivity, in part owing to suppressing proinflammatory gene expressions and improving hepatic lipid metabolism in diabetic mice.

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

“…SCD-1 is conserved among mammalian species. [17] It is modulated by dietary components: high levels of palmitoleic acid inhibit SCD-1 expression and activity, [3,6] while saturated fatty acids, sucrose, fructose, and alcohol are www.advancedsciencenews.com www.mnf-journal.com known inducers and activators of this enzyme. [18] SCD-1 activity has been estimated by the ratio of palmitoleic to palmitic acids (16:1n-7/16:0) in plasma.…”

“…[16] Palmitoleic acid has been described as a powerful blocker (of activity and expression) of SCD-1, reducing insulin resistance and NAFLD in mice. [3,6] The inhibitory effect of palmitoleic acid on SCD-1 expression depends on the tissue, being less pronounced in adipose tissue and greater in liver of FABP knockout mice, which presented high levels of palmitoleic acid, lower de novo hepatic lipogenesis, and resistance to deleterious effects of high fat diet. [3] Similar inhibition of SCD-1 was observed in adipose tissue of type-2 diabetic mice treated with palmitoleic acid, in which this monounsaturated fatty acid increased insulin sensitivity and controlled NAFLD progression.…”

“…[3] Similar inhibition of SCD-1 was observed in adipose tissue of type-2 diabetic mice treated with palmitoleic acid, in which this monounsaturated fatty acid increased insulin sensitivity and controlled NAFLD progression. [6] Thus, in murine models of metabolic disease, the modulation of SCD-1 in adipose tissue promoted by palmitoleic acid may be crucial to the metabolic improvements seen.…”

“…[48] The ability of palmitoleic acid to promote anti-inflammatory effects has been described. [3,4,6,11,14,15,49] In cell cultures, palmitoleic acid was shown to modulate the phenotype of macrophages, reduce expression and production of proinflammatory factors, and block some proinflammatory effects of palmitic acid and LPS [12,14,15,50] (Figure 2). Similarly, supplementation with palmitoleic acid or palmitoleic acid enriched oils reduced inflammation in adipose tissue [26] and liver [4,11] of obese mice fed a high-fat diet.…”

“…[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.…”