Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats

Suchánková, Gabriela; Tekle, Michael; Saha, Asish K.; Ruderman, Neil B.; Clarke, Steven D.; Gettys, Thomas W.

doi:10.1016/j.bbrc.2004.11.114

Cited by 111 publications

(95 citation statements)

References 35 publications

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“…Lipids are the other major energy source for cellular metabolism. Recent studies (10,11) in heart and liver have revealed that AMPK may be sensitive to the "lipid status" of a cell, and activation may be influenced by intracellular fatty acid availability independent of the cellular AMP levels. Indeed, a reduced fat oxidative capacity has been reported in type 2 diabetic patients (12).…”

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confidence: 99%

Activation of Protein Phosphatase 2A by Palmitate Inhibits AMP-activated Protein Kinase

Song

et al. 2007

Journal of Biological Chemistry

250

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Evidence accumulated over the past several years indicates that the AMP-activated protein kinase (AMPK) 2 may be a therapeutic target for treating insulin resistance and type 2 diabetes (1). AMPK is a heterotrimeric protein formed by an ␣ subunit, which contains the catalytic activity, and by the ␤ and ␥ regulatory subunits important in maintaining stability of the heterotrimer complex (2). AMPK belongs to a family of energy-sensing enzymes functioning as a "fuel gauge" that monitors changes in the energy status of a cell (3, 4). When activated, AMPK shuts down anabolic pathways and promotes catabolism in response to an elevated AMP/ATP ratio by down-regulating the activity of several key enzymes of intermediary metabolism (4). Two primary acute consequences of AMPK activation are 1) an increase in glucose uptake by induction of glucose 4 transporter microvesicle cytoplasm to membrane translocation and fusion and 2) an increase in fatty acid oxidation by phosphorylation and inactivation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis (5). Therefore, the AMPK signal pathways are thought to play a central role in the regulation of cellular glucose and lipid homeostasis. The control of AMPK activity is complex, and the classic view is that AMPK is activated allosterically by an increase in the intracellular AMP/ATP ratios and/or by the phosphorylation of threonine 172 within the ␣ subunit. Several protein kinases responsible for this phosphorylation have been identified. They include Peutz-Jeghers syndrome kinase LKB1 (LKB1) (6), and the Ca 2ϩ /calmodulin-dependent protein kinase kinase (7). Protein phosphorylation signal transduction systems are balanced and regulated delicately by both phosphatase and kinase. Since AMPK is activated by (a) protein kinase(s) at the threonine 172 residue, one can easily assume that AMPK can be regulated negatively by (a) serine/threonine phosphatase(s). To date, a wide range of physiological stressors, pharmacological agents, and hormones associated with increase in the intracellular AMP/ATP ratios have been demonstrated to activate AMPK (8). AMPK is also thought to be regulated by glycogen (9), which is the major cellular storage form of carbohydrates and thus, an additional indicator of cellular energy status. Lipids are the other major energy source for cellular metabolism. Recent studies (10, 11) in heart and liver have revealed that AMPK may be sensitive to the "lipid status" of a cell, and activation may be influenced by intracellular fatty BSA, bovine serum albumin; eNOS, endothelial nitric-oxide synthase; LKB1, Peutz-Jeghers syndrome kinase LKB1; OA, okadaic acid; ONOO Ϫ , peroxynitrite; VSMC, vascular smooth muscle cell; siRNA, short interference RNA; FFA, free fatty acid; EBM, endothelial basal medium; 2-BrP, 2-bromopalmitate; HFD, high fat diet; PP2C, protein phosphatase 2C.

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confidence: 99%

Activation of Protein Phosphatase 2A by Palmitate Inhibits AMP-activated Protein Kinase

Song

et al. 2007

Journal of Biological Chemistry

250

220

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“…The decrease of hepatic triacylglycerol production by DHA/EPA may represent a functional outcome of the coordinated suppression of lipogenic genes by n-3 LC-PUFA [17]. In addition, stimulation of AMP-activated protein kinase by n-3 LC-PUFA, resulting in a metabolic switch from lipogenesis to lipid catabolism, may also be involved [49].…”

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confidence: 99%

n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet

et al. 2009

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Aims/hypothesis Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators of peroxisome proliferator-activated receptor γ, which improve wholebody insulin sensitivity. We hypothesised that a combined treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms, impairments of lipid and glucose homeostasis in obesity.Methods Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone (10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as on liver and muscle gene expression and metabolism were analysed. Euglycaemic-hyperinsulinaemic clamps were used to characterise the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose tolerance (IGT). Results DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, Diabetologia (2009) 52:941-951

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“…As with thiazolidinediones, EPA and DHA may upregulate Adipoq by acting as ligands of peroxisome proliferator-activated receptor-γ, the transcriptional regulator interacting directly with Adipoq promoter [8]. The stimulation of Adipoq may also depend on the activation of AMPK, since AMPK in adipocytes stimulates Adipoq [9] and EPA and DHA activate hepatic AMPK [10].…”

Section: Discussionmentioning

confidence: 99%

Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet

et al. 2006

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Aims/hypothesis: Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. Methods: We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. Results: In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. Conclusions/interpretation: Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.

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Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats

Cited by 111 publications

References 35 publications

Activation of Protein Phosphatase 2A by Palmitate Inhibits AMP-activated Protein Kinase

Activation of Protein Phosphatase 2A by Palmitate Inhibits AMP-activated Protein Kinase

n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet

Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet

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