Tingting Guo1, Tomohiro Tanaka2, Mami Matsumoto3, Kentaro Kaneko4, Tomo Unzai4, Yohei Ogino4, Daisuke Aotani5, Toru Kusakabe4, Hiroshi Iwakura4, Takashi Miyazawa4, Kazunobu Sawamoto6, Yasuhiko Minokoshi7, Hiroaki Masuzaki8, Nobuya Inagaki9, Kazuwa Nakao4. 1. Medical Innovation Center, Kyoto University Graduate School of Medicine, 53, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan. 2. Medical Innovation Center, Kyoto University Graduate School of Medicine, 53, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. Electronic address: tttanaka@med.negoya-cu.ac.jp. 3. Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 4. Medical Innovation Center, Kyoto University Graduate School of Medicine, 53, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan. 5. Medical Innovation Center, Kyoto University Graduate School of Medicine, 53, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. 6. Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan; Division of Neural Development and Regeneration, National Institute for Physiological Sciences, Okazaki 444-8585, Japan. 7. Division of Endocrinology and Metabolism, National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, 444-8585, Okazaki, Japan. 8. Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Medicine), Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami-gun, Okinawa, 903-0215, Japan. 9. Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, 54, Shogoin-Kawaharamachi, Sakyo-ku, Kyoto, 606-8507, Japan.
Abstract
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.
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.
Authors: Francisco Navarrete; María S García-Gutiérrez; Ani Gasparyan; Daniela Navarro; Francisco López-Picón; Álvaro Morcuende; Teresa Femenía; Jorge Manzanares Journal: Biomolecules Date: 2022-03-03