Abstract
Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/− heparin (IL, ILH, respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with ILH/SH; and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with ILH/SH. ILH significantly lowered food intake during refeeding compared to SH (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of ILH on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented ILH effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation.
Highlights
The central nervous system (CNS) is a key player in the regulation of energy balance in mammals [1,2]
Since the work by Oomura et al [7], growing evidence suggests that neurons can sense FA and that hypothalamic FA sensing plays a role in the regulation of food intake [3,5]
Despite the fact that intracerebroventricular infusion of oleic acid has been shown to decrease both food intake and hepatic glucose production [11], the idea that an increase in brain FA levels in response to a meal could act as a satiety signal to inhibit feeding appears counterintuitive
Summary
The central nervous system (CNS) is a key player in the regulation of energy balance in mammals [1,2]. Prolonged intracerebroventricular infusion of oleic acid (OA) decreases both food intake and glucose production in rats through a KATP channel dependent mechanism [11]. Both mitochondrial reactive oxygen species [12] and nitric oxide production [13] have been evidenced as mediators for brain lipid sensing in rats. To that end 5 h fasted rats were infused for 10 min with a heparinized triglyceride emulsion (Intralipid, ILH) through carotid artery and spontaneous food intake was monitored over the 5 h of refeeding Such short term carotid infusion of ILH was designed to mimic the increase in TG-enriched lipoproteins to which the brain is exposed post-prandially. We found that acute ILH infusions decreased spontaneous food intake during refeeding independently of b-oxidation but through mechanisms involving both CD36 and acylCoA synthesis
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