Central administrations of palmitic acid and arachidonic acid decrease central leptin sensitivity in mice
Purpose: Leptin inhibits feeding and increases energy expenditure through the central nervous system. High-fat diet with saturated fatty acids (SFA) or n-6 polyunsaturated fatty acids (n-6 PUFA) has been reported to induce central leptin resistance and obesity. However, little is known if central administration of SFA or n-6 PUFA can reduce central leptin sensitivity. This study examined the central leptin sensitivity in response to intracerebroventricular (i.c.v.) injection of SFA, palmitic acid (PA) and n-6 PUFA, arachidonic acid (ARA) in mice. Methods: After overnight fasting, C57BL/6J male mice (n=24/group) were i.c.v. injected with either PA (50pmol/2ul), ARA (50pmol/2ul) or vehicle (saline, 2ul) prior to i.c.v. injection of leptin (0.5ug/2ul) or saline followed by refeeding for 24 hours ad libitum on normal diet. Food intake was measured at 1, 4, 16 and 24 hours after leptin i.c.v. injection. Body weight gain was measured 24 hours after leptin injection. Results: PA and ARA icv injection did not significantly change food intake in mice compared with vehicle group. In vehicle group, central leptin administration significantly suppressed food intake at 1hour (64.60%, p=0.001), 4hour (54.98%, p=0.003), 16hour (54.34%, p
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