Dietetics and Clinical Nutrition | Open Access Articles

The Central Melanocortin System And Human Obesity, Yongjie Yang, Yong Xu

Children’s Nutrition Research Center Staff Publications

The prevalence of obesity and the associated comorbidities highlight the importance of understanding the regulation of energy homeostasis. The central melanocortin system plays a critical role in controlling body weight balance. Melanocortin neurons sense and integrate the neuronal and hormonal signals, and then send regulatory projections, releasing anorexigenic or orexigenic melanocortin neuropeptides, to downstream neurons to regulate the food intake and energy expenditure. This review summarizes the latest progress in our understanding of the role of the melanocortin pathway in energy homeostasis. We also review the advances in the identification of human genetic variants that cause obesity via mechanisms that …

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Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA

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Paraventricular Hypothalamus Mediates Diurnal Rhythm Of Metabolism, Eun Ran Kim, Yuanzhong Xu, Ryan M Cassidy, Yungang Lu, Yongjie Yang, Jinbin Tian, De-Pei Li, Rachel Van Drunen, Aleix Ribas-Latre, Zhao-Lin Cai, Mingshan Xue, Benjamin R Arenkiel, Kristin Eckel-Mahan, Yong Xu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Defective rhythmic metabolism is associated with high-fat high-caloric diet (HFD) feeding, ageing and obesity; however, the neural basis underlying HFD effects on diurnal metabolism remains elusive. Here we show that deletion of BMAL1, a core clock gene, in paraventricular hypothalamic (PVH) neurons reduces diurnal rhythmicity in metabolism, causes obesity and diminishes PVH neuron activation in response to fast-refeeding. Animal models mimicking deficiency in PVH neuron responsiveness, achieved through clamping PVH neuron activity at high or low levels, both show obesity and reduced diurnal rhythmicity in metabolism. Interestingly, the PVH exhibits BMAL1-controlled rhythmic expression of GABA-A receptor γ2 subunit, and dampening …

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Disrupted Hypothalamic Crh Neuron Responsiveness Contributes To Diet-Induced Obesity, Canjun Zhu, Yuanzhong Xu, Zhiying Jiang, Jin Bin Tian, Ryan M Cassidy, Zhao-Lin Cai, Gang Shu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qingyan Jiang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic mainly results from high-fat high-caloric diet (HFD) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress-related diet-induced obesity remains unknown. Corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamus (PVH), a known body weight-regulating region, represent one key group of stress-responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both …

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Parenteral Lipids Shape Gut Bile Acid Pools And Microbiota Profiles In The Prevention Of Cholestasis In Preterm Pigs, Lee Call, Tiffany Molina, Barbara Stoll, Greg Guthrie, Shaji Chacko, Jogchum Plat, Jason Robinson, Sen Lin, Caitlin Vonderohe, Mahmoud Mohammad, Dennis Kunichoff, Stephanie Cruz, Patricio Lau, Muralidhar Premkumar, Jon Nielsen, Zhengfeng Fang, Oluyinka Olutoye, Thomas Thymann, Robert Britton, Per Sangild, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, …

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Estrogen Receptor-Α Expressing Neurons In The Ventrolateral Vmh Regulate Glucose Balance, Yanlin He, Pingwen Xu, Chunmei Wang, Yan Xia, Meng Yu, Yongjie Yang, Kaifan Yu, Xing Cai, Na Qu, Kenji Saito, Julia Wang, Ilirjana Hyseni, Matthew Robertson, Badrajee Piyarathna, Min Gao, Sohaib A Khan, Feng Liu, Rui Chen, Cristian Coarfa, Zhongming Zhao, Qingchun Tong, Zheng Sun, Yong Xu

Children’s Nutrition Research Center Staff Publications

Brain glucose-sensing neurons detect glucose fluctuations and prevent severe hypoglycemia, but mechanisms mediating functions of these glucose-sensing neurons are unclear. Here we report that estrogen receptor-α (ERα)-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH) can sense glucose fluctuations, being glucose-inhibited neurons (GI-ERαvlVMH) or glucose-excited neurons (GE-ERαvlVMH). Hypoglycemia activates GI-ERαvlVMH neurons via the anoctamin 4 channel, and inhibits GE-ERαvlVMH neurons through opening the ATP-sensitive potassium channel. Further, we show that GI-ERαvlVMH neurons preferentially project to the medioposterior arcuate nucleus of the hypothalamus (mpARH) and GE-ERαvlVMH neurons preferentially project to the dorsal Raphe nuclei (DRN). Activation of ERαvlVMH …

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Ampk In The Ventromedial Nucleus Of The Hypothalamus: A Key Regulator For Thermogenesis, Hailan Liu, Yong Xu, Fang Hu

Children’s Nutrition Research Center Staff Publications

Obesity has become a global health issue, but effective therapies remain very limited. Adaptive thermogenesis promotes weight loss by dissipating energy in the form of heat, thereby representing a promising target to counteract obesity. Notably, the regulation of thermogenesis is tightly orchestrated by complex neuronal networks, especially those in the hypothalamus. Recent evidence highlights the importance of adenosine monophosphate-activated protein kinase (AMPK) within the ventromedial nucleus of the hypothalamus (VMH) in modulating thermogenesis. Various molecules, such as GLP-1, leptin, estradiol, and thyroid hormones, have been reported to act on the VMH to inhibit AMPK, which subsequently increases thermogenesis through the …

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Steroid Receptor Coactivator-1 Modulates The Function Of Pomc Neurons And Energy Homeostasis, Yongjie Yang, Agatha A Van Der Klaauw, Liangru Zhu, Tessa M Cacciottolo, Yanlin He, Lukas K J Stadler, Chunmei Wang, Pingwen Xu, Kenji Saito, Antentor Hinton, Xiaofeng Yan, Julia M Keogh, Elana Henning, Matthew C Banton, Audrey E Hendricks, Elena G Bochukova, Vanisha Mistry, Katherine L Lawler, Lan Liao, Jianming Xu, Stephen O'Rahilly, Qingchun Tong, Uk10k Consortium, Inês Barroso, Bert W O'Malley, I Sadaf Farooqi, Yong Xu

Children’s Nutrition Research Center Staff Publications

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function …

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Full-Text Articles in Dietetics and Clinical Nutrition

The Central Melanocortin System And Human Obesity, Yongjie Yang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Paraventricular Hypothalamus Mediates Diurnal Rhythm Of Metabolism, Eun Ran Kim, Yuanzhong Xu, Ryan M Cassidy, Yungang Lu, Yongjie Yang, Jinbin Tian, De-Pei Li, Rachel Van Drunen, Aleix Ribas-Latre, Zhao-Lin Cai, Mingshan Xue, Benjamin R Arenkiel, Kristin Eckel-Mahan, Yong Xu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Disrupted Hypothalamic Crh Neuron Responsiveness Contributes To Diet-Induced Obesity, Canjun Zhu, Yuanzhong Xu, Zhiying Jiang, Jin Bin Tian, Ryan M Cassidy, Zhao-Lin Cai, Gang Shu, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qingyan Jiang, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

Children’s Nutrition Research Center Staff Publications

Children’s Nutrition Research Center Staff Publications

Ampk In The Ventromedial Nucleus Of The Hypothalamus: A Key Regulator For Thermogenesis, Hailan Liu, Yong Xu, Fang Hu

Children’s Nutrition Research Center Staff Publications

Children’s Nutrition Research Center Staff Publications