Eun Roh1,2, Gil Myoung Kang1, So Young Gil1, Chan Hee Lee1, Seongjun Kim1,3, Dugu Hong1,3, Gi Hoon Son4, Min-Seon Kim1,2,5. 1. Appetite Regulation Laboratory, Asan Institute for Life Sciences, Seoul, Korea. 2. Department of Translational Medicine, University of Ulsan College of Medicine, Seoul, Korea. 3. Department of Biomedical Science, University of Ulsan College of Medicine, Seoul, Korea. 4. Department of Biomedical Science, Korea University College of Medicine, Seoul, Korea. 5. Division of Endocrinology and Metabolism, Asan Medical Center, Seoul, Korea.
Abstract
OBJECTIVE: Adequate nicotinamide adenine dinucleotide (NAD) content in hypothalamic neurons is critical for the maintenance of normal energy balance and circadian rhythm. In this study, the beneficial metabolic effects of chronic NAD supplementation on diet-induced obesity and obesity-related disruption of diurnal rhythms were examined. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and received an intraperitoneal injection of either saline or NAD (1 mg/kg/day) for the last 4 weeks. The control mice were fed a chow diet and injected with saline for the same period. Body weights were monitored daily. Daily rhythms of food intake, energy expenditure, and locomotor activity were measured at the end of NAD treatment. The effect of NAD treatment on the clock gene Period 1 (PER1) transcription was also studied. RESULTS: Chronic NAD supplementation significantly attenuated weight gain in HFD-fed obese mice. Furthermore, NAD treatment recovered the suppressed rhythms in the diurnal locomotor activity patterns in obese mice. In addition, exogenous NAD supply rescued cellular NAD depletion-induced suppression of PER1 transcriptional activity in hypothalamic neuron cells as well as blunted daily fluctuations of hypothalamic arcuate nucleus PER1 expression in obese mice. CONCLUSIONS: NAD supplementation showed therapeutic effects in obese mice with altered diurnal behaviors.
OBJECTIVE: Adequate nicotinamide adenine dinucleotide (NAD) content in hypothalamic neurons is critical for the maintenance of normal energy balance and circadian rhythm. In this study, the beneficial metabolic effects of chronic NAD supplementation on diet-induced obesity and obesity-related disruption of diurnal rhythms were examined. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and received an intraperitoneal injection of either saline or NAD (1 mg/kg/day) for the last 4 weeks. The control mice were fed a chow diet and injected with saline for the same period. Body weights were monitored daily. Daily rhythms of food intake, energy expenditure, and locomotor activity were measured at the end of NAD treatment. The effect of NAD treatment on the clock gene Period 1 (PER1) transcription was also studied. RESULTS: Chronic NAD supplementation significantly attenuated weight gain in HFD-fed obesemice. Furthermore, NAD treatment recovered the suppressed rhythms in the diurnal locomotor activity patterns in obesemice. In addition, exogenous NAD supply rescued cellular NAD depletion-induced suppression of PER1 transcriptional activity in hypothalamic neuron cells as well as blunted daily fluctuations of hypothalamic arcuate nucleus PER1 expression in obesemice. CONCLUSIONS:NAD supplementation showed therapeutic effects in obesemice with altered diurnal behaviors.
Authors: Na Xie; Lu Zhang; Wei Gao; Canhua Huang; Peter Ernst Huber; Xiaobo Zhou; Changlong Li; Guobo Shen; Bingwen Zou Journal: Signal Transduct Target Ther Date: 2020-10-07