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7280930 
Journal Article 
A combination of dietary fat intake and nicotine exposure enhances CB1 endocannabinoid receptor expression in hypothalamic nuclei in male mice 
Guo, T; Tanaka, T; Matsumoto, M; Kaneko, K; Unzai, T; Ogino, Y; Aotani, D; Kusakabe, T; Iwakura, H; Miyazawa, T; Sawamoto, K; Minokoshi, Y; Masuzaki, H; Inagaki, N; Nakao, K 
2020 
1 
Neuroscience Letters
ISSN: 0304-3940
EISSN: 1872-7972 
Elsevier Ireland Ltd 
714 
134550 
English 
31634502 
WOS:000502884800014 
BACKGROUND: Cannabinoid receptor 1 (CB1R) is a GPCR expressed widely in the brain as well as in peripheral metabolic organs. Although pharmacological blockade of CB1R has been effective for the treatment of obesity and tobacco addiction, precise distribution of CB1R within the brain and potential changes by obesity or nicotine exposure have not been thoroughly addressed.

METHODS: To examine CB1R distribution within the central energy center, we performed immunostaining and qPCR analysis of micro-dissected hypothalamic nuclei from male C57BL/6 mice. To address the effect of nicotine on food intake and body weight, and on potential changes of CB1R levels in the hypothalamus, mice kept on a high fat diet (HFD) for four weeks were challenged with nicotine intraperitoneally.

RESULTS: Validity of the micro-dissected samples was confirmed by the expression of established nucleus-enriched genes. The expression levels of CB1R in the arcuate and lateral nuclei of the hypothalamus were higher than paraventricular and ventral-dorsal medial nuclei. Nicotine administration led to a significant suppression of food intake and body weight either under standard or high fat diet. Neither HFD nor nicotine alone altered CB1R levels in any nucleus tested. By contrast, treatment of HFD-fed mice with nicotine led to a significant increase in CB1R levels in the arcuate, paraventricular and lateral nuclei.

CONCLUSIONS: CB1R was widely distributed in multiple hypothalamic nuclei. The expression of CB1R was augmented only when mice were treated with HFD and nicotine in combination. These data suggest that the exposure to nicotine may provoke an enhanced endocannabinoid response in diet-induced obesity. 
CB1R; Endocannabinoid; High fat diet; Hypothalamus; Nicotine; Obesity; alpha intermedin; cannabinoid 1 receptor; corticotropin releasing factor; melanocortin 4 receptor; messenger RNA; neuropeptide; nicotine; cannabinoid 1 receptor; corticotropin releasing factor receptor; corticotropin releasing factor receptor 1; neuropeptide Y; nicotine; animal experiment; animal model; animal tissue; Article; body weight; body weight gain; controlled study; energy metabolism; fat intake; hypothalamus nucleus; immunohistochemistry; lipid diet; male; mouse; nonhuman; obesity; priority journal; protein expression; tissue distribution; tobacco dependence; animal; arcuate nucleus; biosynthesis; dorsomedial hypothalamic nucleus; drug effect; eating; hypothalamic paraventricular nucleus; lateral hypothalamus; lipid diet; metabolism; microdissection; procedures; Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Diet, High-Fat; Dorsomedial Hypothalamic Nucleus; Eating; Hypothalamic Area, Lateral; Male; Mice; Microdissection; Neuropeptide Y; Nicotine; Paraventricular Hypothalamic Nucleus; Receptor, Cannabinoid, CB1; Receptors, Corticotropin-Releasing Hormone