Abstract
ObjectivePancreatic-derived factor (PANDER, also named as FAM3B) is secreted by pancreatic α and β cells. Increasing evidence suggests that it may serve a hormonal function related to glycemic and lipid metabolism. In this study, we investigated the effects of PANDER overexpression on hepatic and adipose triglyceride metabolism in high-fat diet-fed male C57BL/6 mice.MethodsPANDER overexpression was achieved by tail-vein injection of recombinant Ad-PANDER and Ad-GFP injected mice served as a control. The TG metabolism in both groups were compared.ResultsAdenoviral-mediated overexpression of PANDER did not affect body weight, food consumption, or liver enzymes. The triglyceride (TG) content of both liver and adipose tissue was significantly decreased in Ad-PANDER mice (liver: 6.16±1.89 mg/g vs. control 14.95±2.27 mg/g, P<0.05; adipose: 39.31±1.99 mg/100mg vs. 47.22±2.21 mg/100mg, P<0.05). The free fatty acid (FFA) content of adipose tissue in Ad-PANDER mice was also decreased (1.38±0.18 mg/g vs. 2.77±0.31 mg/g, P<0.01). The investigation of key enzymes of triglyceride hydrolysis and FFA oxidation in liver and adipose tissue showed that p-HSL/HSL was significantly increased and that DGAT1 gene and protein expression were significantly reduced in the liver of PANDER-overexpressing mice. PKA phosphorylation was also significantly increased in the livers of Ad-PANDER mice. No differences in ATGL, CPT1, ACOX1, or DGAT2 expression were observed.ConclusionOverexpression of PANDER is associated with observable decreases in TG, increases in PKA phosphorylation, and decreased DGAT1 expression, suggesting a possible interrelationship. The mechanisms by which this occurs remain to be elucidated.
Highlights
Triglycerides (TG) are the most abundant lipids in the mammalian body
The investigation of key enzymes of triglyceride hydrolysis and free fatty acid (FFA) oxidation in liver and adipose tissue showed that p-hormone-sensitive lipase (HSL)/HSL was significantly increased and that DGAT1 gene and protein expression were significantly reduced in the liver of PANDER-overexpressing mice
Overexpression of PANDER is associated with observable decreases in TG, increases in protein kinase (PKA) phosphorylation, and decreased DGAT1 expression, suggesting a possible interrelationship
Summary
Triglycerides (TG) are the most abundant lipids in the mammalian body. Nonesterified fatty acids (NEFA), one of the products of TG hydrolysis, are biomolecules that play multiple roles in energy utilization, receptor signaling and/or intracellular signaling. Normal regulation of TG lipolysis and synthesis in liver and white adipose tissue maintains appropriate tissue concentrations of NEFA and whole-body energy homeostasis Enzymes such as acyl-CoA:diacylglycerol acyltransferase (DGAT) in TG synthesis [1], hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in TG mobilization, and carnitine palmitoyltransferase (CPT1) and palmitoyl-CoA oxidase (ACOX1) in fatty acid β-oxidation play essential roles in the regulation of triglyceride metabolism. Their activities are regulated by both hormones and cytokines [2,3,4]
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