Intraperitoneal injections of low doses of C75 elicit a behaviorally specific and vagal afferent-independent inhibition of eating in rats.

Central and intraperitoneal C75, an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyl-transferase-1, inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether intraperitoneal C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts nonselectively, for example by eliciting illness or aversion.

Dissociation of mercaptoacetate's effects on feeding and fat metabolism by dietary medium- and long-chain triacylglycerols in rats.

Objective And Methods: Mercaptoacetate (MA) inhibits hepatic fatty acid oxidation (FAO) and stimulates feeding in rats fed fat-rich diets. To test whether the feeding stimulation by MA depends on hepatic FAO, we compared the effects of intraperitoneally injected MA (45.6 mg/kg body weight) with saline in rats fed diets containing 18% predominately long-chain triacylglycerols (LCTs; > or =90% 16 C) or 18% medium-chain triacylglycerols (MCTs; 51% 10-12 C).

Beta-adrenergic-mediated inhibition of feeding by mercaptoacetate in food-deprived rats.

This study investigated the effect of intraperitoneal (IP) injections of the fatty acid oxidation (FAO) inhibitor mercaptoacetate (MA, 45.6 mg/kg) on feeding in food-deprived rats. As previously, MA significantly stimulated feeding in ad libitum-fed rats.

Vagal afferents mediate the feeding response to mercaptoacetate but not to the beta (3) adrenergic receptor agonist CL 316,243.

To evaluate the role of subdiaphragmatic vagal afferents in the anorectic response to peripheral administration of the highly selective beta(3)-adrenergic receptor agonist CL 316,243 (CL), we tested the ability of intraperitoneal (IP) injections of CL to inhibit feeding in rats with subdiaphragmatic vagal deafferentation (SDA, n=13) or sham surgeries (SHAM, n=13). Doses of 10, 100 and 1000 ng/kg CL significantly reduced feeding by statistically similar amounts in SHAM and SDA rats. One hour after IP injection, each dose of CL also significantly increased plasma concentrations of free fatty acids and beta-hydroxybutyrate, an indicator of hepatic fatty acid oxidation (FAO), whereas 6h after injection only the two highest CL doses increased plasma beta-hydroxybutyrate.

Hepatic-portal oleic acid inhibits feeding more potently than hepatic-portal caprylic acid in rats.

In several human and animal studies, medium-chain triglycerides decreased food intake more than did long-chain triglycerides. It is possible that faster uptake and metabolism of medium-chain fatty acids in the liver is responsible for this difference. To test this hypothesis we compared the feeding effects of hepatic portal vein (HPV) infusion of the medium-chain fatty acid caprylic acid (CA) with those of the long-chain fatty acid oleic acid (OA).

Mercaptoacetate fails to block the feeding-inhibitory effect of the beta3-adrenergic receptor agonist CGP 12177A.

Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.

Beneficial and deleterious effects of hydroxycitrate in rats fed a high-fructose diet.

Objective: The present study assessed whether long-term supplementation of a high-fructose diet with hydroxycitrate (HCA), an inhibitor of de novo lipogenesis that is widely used as a non-prescription dietary aid, decreases food intake, visceral fat accumulation, hypertriglyceridemia, and hyperinsulinemia in rats.

Methods: We examined the effects of HCA (1.8% of diet) on food intake, body weight gain, visceral fat accumulation, hypertriglyceridemia, and hyperinsulinemia in rats during a 4-wk period of ad libitum access to a 50% fructose diet after a 3-wk period of food restriction in which they lost about 20% of their body weight.

Caprylic acid infusion acts in the liver to decrease food intake in rats.

Hepatic portal vein (HPV) infusion of the medium chain fatty acid caprylic acid (CA; 2.3 mg/min, 40 microl/min) for 90 min beginning at dark onset in 18-h food-deprived male rats reduced the size of the first nocturnal meal about 40% (P < 0.01) and reduced 24-h food intake by about 15% (P < 0.

CPT1alpha over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells.

To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1alpha (CPT1alpha). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1alpha transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7.

Fatty acid oxidation and control of food intake.

Fatty acid oxidation is thought to play a role in the control of food intake, and a low postprandial oxidation of ingested fat may contribute to the overeating on a high-fat diet. Evidence for a role of fatty acid oxidation in control of food intake is mainly derived from the stimulation of feeding in response to administration of the acyl-CoA-dehydrogenase inhibitor mercaptoacetate (MA) and other inhibitors of fatty acid oxidation in different species (rat, mouse, man). Denervation studies suggest that this "lipoprivic feeding" is related to changes in hepatic fatty acid oxidation.

Effect of hydroxycitrate on respiratory quotient, energy expenditure, and glucose tolerance in male rats after a period of restrictive feeding.

Objective: Recently we demonstrated that hydroxycitrate (HCA) suppresses food intake and body weight regain in male rats after substantial body weight loss. However, it is not known whether HCA also affects the respiration quotient (RQ), energy expenditure (EE), and glucose tolerance in this animal model.

Methods: Twenty-four male rats (initial body weight, 378 +/- 3 g) were fed restrictively (10 g/d) for 10 d and then given ad libitum access to a high-glucose diet supplemented with 3% HCA for 6 d.

Subdiaphragmatic vagal deafferentation fails to block the anorectic effect of hydroxycitrate.

We investigated the neural mediation of the feeding suppression through orally administered hydroxycitrate (HCA) in male rats that were fed a high-glucose diet (about 48% glucose). Ten-day ad libitum food intake and body weight regain after previous body weight loss (13% of initial body weight) due to restrictive feeding were measured in rats with sham deafferentation (SHAM; n = 6), subdiaphragmatic vagal deafferentation (SDA; n = 7), and SDA plus celiac-superior mesenteric ganglionectomy (SDA/CGX; n = 9). HCA suppressed the 10-day cumulative food intake in all surgical groups and body weight regain in SDA and SDA/CGX groups.

Hydroxycitrate has long-term effects on feeding behavior, body weight regain and metabolism after body weight loss in male rats.

We examined the long-term effect of hydroxycitrate (HCA) on food intake, meal patterns, body weight regain and energy conversion ratio as well as on different blood and liver variables in rats after substantial body weight loss. Rats were fed a 1% (g/100 g) fat diet (81% carbohydrate, 10% protein, 1% fat) or a 12% (g/100 g) fat diet (76% carbohydrate, 9% protein, 12% fat) in two separate experiments. Supplementing both diets with 3% HCA after 10 d of restrictive feeding reduced body weight regain over the whole subsequent period of ad libitum consumption (22 d) and decreased the energy conversion ratio [body weight regain (g)/energy intake (MJ)] at the end of the experiment.