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Endocrinology & Metabolism
Hailan Liu, Yang He, Juli Bai, Chuanhai Zhang, Feng Zhang, Yongjie Yang, Hairong Luo, Meng Yu, Hesong Liu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Zili Yan, Nikolas Anthony Scarcelli, Kristine Marie Conde, Mengjie Wang, Jonathan Carter Bean, Camille Hollan Sidell Potts, Chunmei Wang, Fang Hu, Feng Liu, Yong Xu
Summary: A study found that the adaptor protein Grb10 can enhance leptin signaling and reduce appetite through regulating the activity of AgRP and POMC neurons. Overexpression of Grb10 in AgRP neurons can decrease body weight, while in POMC neurons it can attenuate diet-induced obesity. The mechanism may involve enhancing leptin's effects on neurons through regulating KATP and TRP channels.
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Biochemistry & Molecular Biology
Qin Tang, Qinhui Liu, Xuping Yang, Tong Wu, Cuiyuan Huang, Jinhang Zhang, Zijing Zhang, Guorong Zhang, Yingnan Zhao, Jian Zhou, Hui Huang, Yan Xia, Jiamin Yan, Yanping Li, Jinhan He
Summary: Overexpression of Sirt6 in hypothalamic POMC neurons exacerbates diet-induced obesity and metabolic disorders, leading to increased adiposity and decreased energy expenditure.
Article
Cell Biology
Yongjie Yang, Yanlin He, Hailan Liu, Wenjun Zhou, Chunmei Wang, Pingwen Xu, Xing Cai, Hesong Liu, Kaifan Yu, Zhou Pei, Ilirjana Hyseni, Makoto Fukuda, Qingchun Tong, Jianming Xu, Zheng Sun, Bert W. O'Malley, Yong Xu
Summary: SRC-2 in POMC neurons is a key regulator of responses to fasting, with specific deletion leading to inadequate suppression of energy expenditure, impaired counterregulation, and insufficient refeeding. These mutant mice also show enhanced satiation, discoordination of anxiety and food-seeking behavior when food becomes available.
Article
Endocrinology & Metabolism
Shengnan Zhou, Weijie Chen, Xuesong Bai, Jiemin Chen, Qiang Xu, Liangbo Dong, Wei Chen, Qiang Qu, Xiaodong He
Summary: This study found that hypothalamic POMC neurons were upregulated after biliary diversion, and increased taurocholic acid (TCA), taurodeoxycholic acid (TDCA), and the gut-derived hormone FGF15 may activate POMC neurons.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cell Biology
Sara Ramirez, Roberta Haddad-Tovolli, Marija Radosevic, Miriam Toledo, Adriana Pane, Daniel Alcolea, Vicent Ribas, Maria Mila-Guasch, Macarena Pozo, Arnaud Obri, Elena Eyre, Alicia G. Gomez-Valades, Inigo Chivite, Tomas Van Eeckhout, Ioannis Zalachoras, Jordi Altirriba, Corinna Bauder, Monica Imbernon, Gloria Garrabou, Carmen Garcia-Ruiz, Ruben Nogueiras, David Soto, Xavier Gasull, Carmen Sandi, Jens C. Bruening, Juan Fortea, Amanda Jimenez, Jose C. Fernandez-Checa, Marc Claret
Summary: Obesity and type 2 diabetes are associated with cognitive dysfunction. This study found that specific neurons in the hypothalamus play an important role in the interface of metabolism and cognition. Acute obesogenic diet administration in mice impaired recognition memory due to defective production of the neurosteroid precursor pregnenolone in the hypothalamus. Our data suggest that pregnenolone's effects on cognitive function were mediated via an autocrine mechanism on POMC neurons, influencing hippocampal long-term potentiation. The relevance of central pregnenolone on cognition was also confirmed in metabolically unhealthy patients with obesity.
Article
Multidisciplinary Sciences
Wen Z. Yang, Hengchang Xie, Xiaosa Du, Qian Zhou, Yan Xiao, Zhengdong Zhao, Xiaoning Jia, Jianhui Xu, Wen Zhang, Shuang Cai, Zhangjie Li, Xin Fu, Rong Hua, Junhao Cai, Shuang Chang, Jing Sun, Hongbin Sun, Qingqing Xu, Xinyan Ni, Hongqing Tu, Ruimao Zheng, Xiaohong Xu, Hong Wang, Yu Fu, Liming Wang, Xi Li, Haitao Yang, Qiyuan Yao, Tian Yu, Qiwei Shen, Wei L. Shen
Summary: The neural pathways responsible for cold defense regulation are still unclear. In this study, the authors found that there are parallel thermogenic pathways from the brainstem to the hypothalamus that work together to enable resilience to cold temperature exposure and hypothermia. These pathways are crucial for cold defense and can induce strong cold-defense responses.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Gil Myoung Kang, Se Hee Min, Chan Hee Lee, Ji Ye Kim, Hyo Sun Lim, Min Jeong Choi, Saet-Byel Jung, Jae Woo Park, Seongjun Kim, Chae Beom Park, Hong Dugu, Jong Han Choi, Won Hee Jang, Se Eun Park, Young Min Cho, Jae Geun Kim, Kyung-Gon Kim, Cheol Soo Choi, Young-Bum Kim, Changhan Lee, Minho Shong, Min-Seon Kim
Summary: The study demonstrates that low-grade mitochondrial stress can influence health and longevity through different metabolic effects on hypothalamic POMC neurons. Modulating mitochondrial ribosomal stress levels can impact obesity in mice, with thermogenesis and mitochondrial unfolded protein responses playing key roles. The findings suggest that POMC neuronal mitohormesis may be the basis of exercise-induced high-turnover metabolism.
Article
Biochemistry & Molecular Biology
Dasol Kang, Hye Rim Yang, Dong Hee Kim, Kwang Kon Kim, Bora Jeong, Byong Seo Park, Jeong Woo Park, Jae Geun Kim, Byung Ju Lee
Summary: TTF-1 stimulates appetite by regulating the expression of AgRP and POMC genes. Sirt1, a NAD(+)-dependent deacetylase, activates TTF-1 in response to energy deficiency. This activation leads to the deacetylation of TTF-1 and its nuclear translocation, enhancing the control of AgRP and POMC gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yanni Zhang, Qiulei Xi, Ming Zhong, Yi Jiang, Qiulin Zhuang, Zuoyou Ding, Shanjun Tan, Junjie Wang, Hao Liu, Zhige Zhang, Ben Zhou, Guohao Wu
Summary: Cachexia is common in cancer patients and its molecular basis is still unclear. This study investigated the regulatory pathway of tumors on appetite-inhibiting neurons (POMC) in the hypothalamus. Results showed that the tumor-expressed SEMA3D is positively related to POMC expression. Knocking out SEMA3D in mice increased food intake and body weight, and reduced muscle and fat catabolism. SEMA3D enhances POMC neuron activity by activating NRP2 and PlxnD1 expression. This research reveals that SEMA3D may play a vital role in appetite suppression and catabolic metabolism.
Article
Medicine, Research & Experimental
Isabella Gaziano, Svenja Corneliussen, Nasim Biglari, Rene Neuhaus, Linyan Shen, Tamara Sotelo-Hitschfeld, Paul Klemm, Lukas Steuernagel, Alain J. De Solis, Weiyi Chen, F. Thomas Wunderlich, Peter Kloppenburg, Jens C. Bruening
Summary: This study reveals the differential effects of dopamine on neurons in the hypothalamic arcuate nucleus, with activation of food intake-promoting neurons and inhibition of anorexigenic neurons. By targeting specific POMC neurons, it is found that dopamine-mediated inhibition of feeding depends on the Drd2 receptor, and POMCDrd2+ neurons exhibit differential expression of neuropeptide signaling mediators. Chemogenetic activation of POMCDrd2+ neurons can suppress feeding and maintain body temperature.
Article
Endocrinology & Metabolism
Cheng Li, Jing-Jing Xu, Hong-Tao Hu, Chao-Yi Shi, Chuan-Jin Yu, Jian-Zhong Sheng, Yan-Ting Wu, He-Feng Huang
Summary: Exposure to maternal HFD can lead to obesity and metabolic disorders in male offspring, but has minimal effects on female offspring. Deficiency of Ramp3 in the fetal hypothalamus might contribute to hyperamylinemia in male offspring exposed to maternal HFD.
MOLECULAR METABOLISM
(2021)
Review
Endocrinology & Metabolism
Pamela Mattar, Lilian Toledo-Valenzuela, Maria Paz Hernandez-Caceres, Daniel Pena-Oyarzun, Eugenia Morselli, Claudio Perez-Leighton
Summary: Excess dietary sucrose is associated with obesity and metabolic diseases, and this may be attributed to the dysregulation of autophagy, which disrupts the function of hypothalamic neurons and white adipose tissue. This disruption leads to increased caloric intake and body weight, favoring the development of obesity and metabolic diseases.
Article
Cell Biology
Ya Liu, Yi-Fan Guo, Hui Peng, Hai-yan Zhou, Tian Su, Mi Yang, Qi Guo, Xiao Ye, Yan Huang, Tie-Jian Jiang
Summary: This study demonstrated that decreased Hnscr in htNSCs led to systematic glucose imbalance through activating NF-kappa B signal and dampening insulin signal in hypothalamic neurons.
CELL PROLIFERATION
(2023)
Article
Neurosciences
Yi-Chun Liao, Yeou San Lim, Pei-Wen Chu, Shau-Kwaun Chen
Summary: Inflammation affects mitochondrial functions and neuronal activities in the hypothalamic POMC neurons. Short to midterm exposure to inflammatory environments stimulates metabolic switch and neuronal activation, while chronic exposure leads to elevated oxidative stress and compromised mitochondrial respiration.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Alexandre Moura-Assis, Pedro A. S. Nogueira, Jose C. de-Lima-Junior, Fernando M. Simabuco, Joana M. Gaspar, Jose Donato Jr, Licio A. Velloso
Summary: The knockdown of TLR4-interactor with leucine-rich repeats (Tril) reduces hypothalamic inflammation, increases whole-body energy expenditure, and improves systemic glucose tolerance to protect against diet-induced obesity. Knockdown of Tril in POMC neurons results in decreased body fat, reduced white adipose tissue inflammation, and a trend towards increased leptin signaling. Tril is identified as a new component in the mechanisms promoting hypothalamic dysfunction in experimental obesity, presenting a novel target for obesity treatment.
SCIENTIFIC REPORTS
(2021)