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M K Grace

Publications and source records attributed to M K Grace.

24 records · Page 2Linked to original sources

Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

Neuropeptide Y administered intracerebroventricularly and into the paraventricular nucleus of the hypothalamus stimulates feeding and decreases brown adipose tissue thermogenesis. Although specific neuropeptide Y antagonists are not yet available, previous studies had shown that the opioid antagonist naloxone blocked neuropeptide Y-induced feeding when both drugs were injected intracerebroventricularly. We wanted to find out if naloxone injected into specific brain sites would block neuropeptide Y effects on feeding and brown fat thermogenesis. Rats were double injected in specific brain sites with neuropeptide Y and either naloxone or naltrexone (a congener of naloxone). Food intake and brown fat measures were assessed. Naloxone or naltrexone in the paraventricular nucleus weakly decreased paraventricular nucleus neuropeptide Y-induced feeding and did not affect neuropeptide Y-induced reductions in brown fat activity. Peripheral naloxone blocked intracerebroventricular neuropeptide Y-induced feeding and brown fat alterations. Fourth ventricular naloxone decreased paraventricular nucleus neuropeptide Y-induced feeding, and naltrexone given into the nucleus of the solitary tract blocked paraventricular nucleus neuropeptide Y-induced alterations in feeding and brown fat. These data indicate that neuropeptide Y in the paraventricular nucleus may act on feeding and brown fat thermogenesis through opioidergic pathways in the nucleus of the solitary tract.

Adipose Tissue, Brown↗

Preference and diet type affect macronutrient selection after morphine, NPY, norepinephrine, and deprivation.

The orexigenic agents morphine, neuropeptide Y (NPY), and norepinephrine (NE) and deprivation have been reported to induce selection of specific macronutrients: fat, carbohydrate (CHO), CHO, and fat, respectively. We utilized analysis of covariance to compensate for the influence of baseline preference on feeding induced by six experimental procedures: morphine, NPY, NE, 24 and 48 h food deprivation, and chronic dietary restriction. Rats received one of two dietary regimens: three macronutrient diets containing CHO, protein, or fat (regimen I) and two nutritionally complete diets that were high CHO or high fat (regimen II). Baseline preference significantly influenced dietary selection after all six experimental procedures studied in regimen I and after NPY, NE, 48 h food deprivation, and chronic dietary restriction in regimen II (covariate P < 0.05). In both dietary regimens, morphine (5 mg/kg) increased consumption of fat, NPY (5 micrograms icv) increased selection of CHO, and consumption of all diets was induced equally after NE injections (20 micrograms icv). After 24 or 48 h food deprivation, animals consumed more fat in regimen I and more CHO diet in regimen II. Restricting food intake by 20% increased fat and protein consumption in regimen I but had no effect in regimen II. Diet selection is affected by prior preference, feeding stimulus, and type of diet choice presented.

Analysis of Variance↗

Rat hypothalamic NPY mRNA and brown fat uncoupling protein mRNA after high-carbohydrate or high-fat diets.

We measured the influence of diet composition on hypothalamic neuropeptide Y (NPY) message and brown fat uncoupling protein (UCP) mRNA using different diets. Sprague-Dawley rats ate ad libitum either chow, a high-carbohydrate (HC), an intermediate-carbohydrate (IHC), a high-fat (HF), or an intermediate-fat (IHF) diet, all with equal protein content (g/kcal). The HF and IHF groups ate less food mass and, except for HC, all groups consumed similar kilocalories during the study. After 1 wk, we killed the animals and extracted total RNA from arcuate nucleus, cortex, and brown adipose tissue (BAT). Arcuate NPY mRNA in the HF group was significantly (P < 0.001) lower than in the HC and chow group. There were no differences between groups in NPY message in cortex or NPY protein in the paraventricular nucleus. BAT UCP message levels were significantly higher (P = 0.001) in the HF group. Thus HF compared with HC and chow diet reduces expression of NPY mRNA in hypothalamic nuclei and increases expression of BAT UCP message.

Adipose Tissue, Brown↗

The effect of norbinaltorphimine, beta-funaltrexamine and naltrindole on NPY-induced feeding.

The non-selective opioid receptor antagonist naloxone decreases the robust feeding observed after i.c.v. injection of neuropeptide Y (NPY). In the present study we evaluated the effects of three selective opioid receptor antagonists on NPY-induced feeding. Graded doses of norbinaltorphimine (norBNI), beta-funaltrexamine (beta-FNA) and naltrindole (NTI), antagonists of the kappa, mu and delta receptors respectively, were preinjected (i.c.v.) in male rats prior to injection of 5 micrograms NPY (i.c.v.). Food intake was measured 1, 2 and 4 h post-NPY injection. Injection of beta-FNA and norBNI were most effective in reducing NPY-induced feeding, whereas NTI had little effect on NPY-induced feeding.

Animals↗

Naloxone's anorectic effect is dependent upon the relative palatability of food.

It has been suggested that opioids modify food intake by enhancing palatability. In the present series of studies we evaluated the effect of naloxone on food intake of a preferred food (chocolate chip cookies), normal rat chow, and an "aversive" food (high fiber chow). We found that naloxone decreased 18- and 48-h deprivation-induced intake of chocolate chip cookies much more potently than that of chow, when these foods were presented on separate occasions. When these foods were presented concurrently, this difference in naloxone's potency was no longer apparent. When rats were offered high fiber chow, only the 10 mg/kg dose of naloxone decreased intake. In these same rats naloxone significantly decreased normal chow intake at a dose of 0.1 mg/kg. Thus, naloxone's ability to decrease food intake appears to be dependent upon the palatability of the food.

Animals↗

Effect of breakfast cereals on short-term food intake.

We evaluated the effect of high-fiber cereals on short-term food intake. At 0730, 14 subjects ingested one of five cereals, plus milk and orange juice. At 1100 they were presented with a buffet lunch. There was a significant inverse correlation between fiber content of the cereals and energy intake at lunch. In a second study subjects ingested a very-high-fiber (VHF) cereal or a very-low-fiber (VLF) cereal. Fewer kcalories were ingested at lunch after ingestion of the VHF cereal than after ingestion of the VLF cereal. The degree of colonic microbial fermentation of the various cereals was evaluated by breath-hydrogen analysis. The higher-fiber cereals resulted in greater hydrogen production; however, this may not influence energy intake. The results of questionnaires that asked about hunger indicated that food intake can be reduced without the perception of feeling less hungry. Thus, we found that cereals containing relatively large quantities of dietary fiber may decrease short-term food intake.

Adult↗