Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling

Abstract

Leptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibility, we examined the effects of chronic central administration of leptin on the expression of key markers of lipid metabolism and its possible relationship with changes in inflammatory- and insulin-signaling pathways in epididymal adipose tissue. Circulating non-esterified fatty acids and pro- and anti-inflammatory cytokines were also measured. Fifteen male rats were divided into control (C), leptin (L, icv, 12 μg/day for 14 days), and pair-fed (PF) groups. We found a decrease in the activity of glucose-6-phosphate dehydrogenase and malic enzyme in the L group, with no changes in the expression of lipogenic enzymes. A reduction in the expression of lipoprotein lipase and carnitine palmitoyl-transferase-1A, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern, were detected in the epididymal fat of L rats. In conclusion, the decrease in insulin sensitivity and increased pro-inflammatory environment could regulate lipid metabolism, reducing epididymal fat stores in response to central leptin infusion.

New Insights into Adipose Tissue Metabolic Function and Dysfunction

“…Furthermore, leptin administration induced a reduction in lipoprotein lipase and carnitine palmitoyl-transferase-1A expression, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern. In conclusion, they demonstrated that central leptin infusion regulated lipid metabolism, reducing epididymal fat stores and suggesting its use as a modulating agent in obesity [ 10 ]. Finally, in a very interesting paper, Di Maio and colleagues evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, and Irisin, a myokine that is stimulated by muscular exercises, to induce the browning process of white adult adipocytes obtained from differentiated mesenchymal stromal cells (MSCs).…”