Altered hypothalamic signaling and responses to food deprivation in rats fed a low-carbohydrate diet.
OBJECTIVE
To model how consuming a low-carbohydrate (LC) diet influences food intake and body weight.


METHODS
Food intake and body weight were monitored in rats with access to chow (CH), LC-high-fat (HF), or HF diets. After 8 weeks, rats received intracerebroventricular injections of a melanocortin agonist (melanotan-II) and antagonist (SHU9119), and feeding responses were measured. At sacrifice, plasma hormones and hypothalamic expression of mRNA for proopiomelanocortin (POMC), melanocortin-4 receptor, neuropeptide Y (NPY), and agouti related protein (AgRP) were assessed. A second set of rats had access to diet (chow or LC-HF) for 4 weeks followed by 24 h food deprivation on two occasions, after which food intake and hypothalamic POMC, NPY, and AgRP mRNA expression were measured.


RESULTS
HF rats consumed more food and gained more weight than rats on CH or LC-HF diets. Despite similar intakes and weight gains, LC-HF rats had increased adiposity relative to CH rats. LC-HF rats were more sensitive to melanotan-II and less sensitive to SHU9119. LC-HF rats had increased plasma leptin and ghrelin levels and decreased insulin levels, and patterns of NPY and POMC mRNA expression were consistent with those of food-deprived rats. LC-HF rats did not show rebound hyperphagia after food deprivation, and levels NPY, POMC, and AgRP mRNA expression were not affected by deprivation.


CONCLUSIONS
Our results demonstrate that an LC diet influences multiple systems involved in the controls of food intake and body weight. These data also suggest that maintenance on an LC-HF diet affects food intake by reducing compensatory responses to food deprivation.
Kinzig
Kimberly P
KP
Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, Maryland, USA. kkinzig@psych.purdue.edu
Scott
Karen A
KA
Hyun
Jayson
J
Bi
Sheng
S
Moran
Timothy H
TH
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D005508:Food Deprivation; D054439:Ghrelin; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D036361:Peptide Hormones / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D036361:Peptide Hormones; D012333:RNA, Messenger; D020155:3-Hydroxybutyric Acid