scholarly journals Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight

2008 ◽  
Vol 294 (2) ◽  
pp. R352-R361 ◽  
Author(s):  
Susan Aja ◽  
Leslie E. Landree ◽  
Amy M. Kleman ◽  
Susan M. Medghalchi ◽  
Aravinda Vadlamudi ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fatty Acid ◽  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Fatty Acid Synthase ◽  
Intraperitoneal Administration ◽  
Carnitine Palmitoyl Transferase ◽  
Dose Dependent

Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1–56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.

Level of satiety: in vitro energy metabolism in brain during hypophagic and hyperphagic body weight recovery

1989 ◽  
Vol 257 (6) ◽  
pp. R1322-R1327 ◽  
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Area Postrema ◽  
Tube Feeding ◽  
Acid Oxidation

Rates of in vitro glucose and fatty acid oxidation were examined in four brain sites during hypophagic and hyperphagic recovery of normal body weight. Rats were fed 40, 100, or 160% of normal intake, via gastric intubation, for 3 wk. Another group of rats was starved until body weight loss was equivalent to weight loss in 40%-fed rats. Groups of rats were killed at the conclusion of tube feeding or fasting and at specific periods during recovery of body weight. Brain sites examined were the ventrolateral hypothalamus (VLH), ventromedial hypothalamus (VMH), a caudal brain stem site encompassing the area postrema-nucleus of the solitary tract (AP-NTS), and cortex. During recovery, rats previously fed 160% of normal intake (anorectic) maintained low rates of VLH fatty acid oxidation and were hypophagic until most excess fat was depleted. Conversely, rats previously fed 40% of normal intake (hungry) maintained high rates of VLH fatty acid oxidation and were hyperphagic until most deficient fat was repleted. Rats previously starved maintained high rates of VLH fatty acid oxidation during hyperphagic recovery, although levels of VLH fatty acid oxidation and food intake were initially low on refeeding. Rates of glucose oxidation in the brain sites examined did not relate well to energy balance status and the needed adjustments in food intake. The results indicated that the level of glucose oxidation in the VLH and AP-NTS responded to the level of energy immediately coming into the system (food intake).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight

2008 ◽  
Vol 105 (4) ◽  
pp. 1550-1559 ◽  
Author(s):  
Michael J. Wolfgang ◽  
Seung Hun Cha ◽  
David S. Millington ◽  
Gary Cline ◽  
Gerald I. Shulman ◽  
...  
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Carnitine Palmitoyl Transferase

scholarly journals Comparison of Central and Peripheral Administration of C75 on Food Intake, Body Weight, and Conditioned Taste Aversion

Diabetes ◽  
2002 ◽  
Vol 51 (11) ◽  
pp. 3196-3201 ◽  
Author(s):  
D. J. Clegg ◽  
M. D. Wortman ◽  
S. C. Benoit ◽  
C. C. McOsker ◽  
R. J. Seeley
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion

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

2008 ◽  
Vol 295 (3) ◽  
pp. R799-R805 ◽  
Author(s):  
Abdelhak Mansouri ◽  
Susan Aja ◽  
Timothy H. Moran ◽  
Gabriele Ronnett ◽  
Francis P. Kuhajda ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Fatty Acid Synthase ◽  
Inhibitory Effect ◽  
Meal Size ◽  
Vagal Afferents ◽  
Low Doses ◽  
Carnitine Palmitoyl Transferase ◽  
Specific Manner ◽  
Vagal Afferent

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. Another issue relates to whether intraperitoneal C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of intraperitoneal C75 on spontaneous meal patterns and the formation of conditioned taste aversion (CTA). We also tested whether the eating inhibitory effect of intraperitoneal C75 is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). Intraperitoneal injection of 3.2 and 7.5 mg/kg of C75 significantly reduced food intake 3, 12, and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg of C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. The eating inhibitory effect of C75 was not diminished in either TVX or SDA rats. We conclude that intraperitoneal injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents.

scholarly journals AM 251 produces sustained reductions in food intake and body weight that are resistant to tolerance and conditioned taste aversion

2006 ◽  
Vol 147 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Adam P Chambers ◽  
Henry S Koopmans ◽  
Quentin J Pittman ◽  
Keith A Sharkey
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion
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