Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus
Cell Metab. 2024 Feb 6;36(2):438-453.e6. doi: 10.1016/j.cmet.2024.01.003.ABSTRACTThe hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the P...
Source: Cell Metabolism - February 7, 2024 Category: Cytology Authors: Ying Lei Xian Liang Yunong Sun Ting Yao Hongyu Gong Zhenhua Chen Yuanqing Gao Hui Wang Ru Wang Yunqi Huang Tao Yang Miao Yu Longqi Liu Chun-Xia Yi Qing-Feng Wu Xingxing Kong Xun Xu Shiping Liu Zhi Zhang Tiemin Liu Source Type: research
GDF15 is a major determinant of ketogenic diet-induced weight loss
Cell Metab. 2024 Feb 6;36(2):454-456. doi: 10.1016/j.cmet.2024.01.004.NO ABSTRACTPMID:38325339 | DOI:10.1016/j.cmet.2024.01.004 (Source: Cell Metabolism)
Source: Cell Metabolism - February 7, 2024 Category: Cytology Authors: Jun Feng Lu Meng Qing Zhu Bo Xia Na Na Zhang Xiao Peng Liu Huan Liu Rui Xin Zhang Jun Ying Xiao Hui Yang Ying Qi Zhang Xiao Miao Li Jiang Wei Wu Source Type: research
Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells
Cell Metab. 2024 Jan 30:S1550-4131(24)00008-1. doi: 10.1016/j.cmet.2024.01.008. Online ahead of print.ABSTRACTSevere forms of malaria are associated with systemic inflammation and host metabolism disorders; however, the interplay between these outcomes is poorly understood. Using a Plasmodium chabaudi model of malaria, we demonstrate that interferon (IFN) γ boosts glycolysis in splenic monocyte-derived dendritic cells (MODCs), leading to itaconate accumulation and disruption in the TCA cycle. Increased itaconate levels reduce mitochondrial functionality, which associates with organellar nucleic acid release and MODC restr...
Source: Cell Metabolism - February 7, 2024 Category: Cytology Authors: Theresa Ramalho Patricia A Assis Ogooluwa Ojelabi Lin Tan Brener Carvalho Luiz Gardinassi Osvaldo Campos Philip L Lorenzi Katherine A Fitzgerald Cole Haynes Douglas T Golenbock Ricardo T Gazzinelli Source Type: research
PHLDA2-mediated phosphatidic acid peroxidation triggers a distinct ferroptotic response during tumor suppression
Cell Metab. 2024 Jan 29:S1550-4131(24)00005-6. doi: 10.1016/j.cmet.2024.01.006. Online ahead of print.ABSTRACTAlthough the role of ferroptosis in killing tumor cells is well established, recent studies indicate that ferroptosis inducers also sabotage anti-tumor immunity by killing neutrophils and thus unexpectedly stimulate tumor growth, raising a serious issue about whether ferroptosis effectively suppresses tumor development in vivo. Through genome-wide CRISPR-Cas9 screenings, we discover a pleckstrin homology-like domain family A member 2 (PHLDA2)-mediated ferroptosis pathway that is neither ACSL4-dependent nor requires...
Source: Cell Metabolism - February 3, 2024 Category: Cytology Authors: Xin Yang Zhe Wang Svetlana N Samovich Alexander A Kapralov Andrew A Amoscato Vladimir A Tyurin Haider H Dar Zhiming Li Shoufu Duan Ning Kon Delin Chen Benjamin Tycko Zhiguo Zhang Xuejun Jiang H ülya Bayir Brent R Stockwell Valerian E Kagan Wei Gu Source Type: research
Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8 < sup > + < /sup > T cells
Cell Metab. 2024 Jan 23:S1550-4131(24)00006-8. doi: 10.1016/j.cmet.2024.01.005. Online ahead of print.ABSTRACTTumors employ diverse strategies for immune evasion. Unraveling the mechanisms by which tumors suppress anti-tumor immunity facilitates the development of immunotherapies. Here, we have identified tumor-secreted fibroblast growth factor 21 (FGF21) as a pivotal immune suppressor. FGF21 is upregulated in multiple types of tumors and promotes tumor progression. Tumor-secreted FGF21 significantly disrupts anti-tumor immunity by rewiring cholesterol metabolism of CD8+T cells. Mechanistically, FGF21 sustains the hyperact...
Source: Cell Metabolism - February 3, 2024 Category: Cytology Authors: Cegui Hu Wen Qiao Xiang Li Zhi-Kun Ning Jiang Liu Sumiya Dalangood Hanjun Li Xiang Yu Zhen Zong Zhenke Wen Jun Gui Source Type: research
Reproductive risk factors across the female lifecourse and later metabolic health
Cell Metab. 2024 Feb 6;36(2):240-262. doi: 10.1016/j.cmet.2024.01.002. Epub 2024 Jan 26.ABSTRACTMetabolic health is characterized by optimal blood glucose, lipids, cholesterol, blood pressure, and adiposity. Alterations in these characteristics may lead to the development of type 2 diabetes mellitus or dyslipidemia. Recent evidence suggests that female reproductive characteristics may be overlooked as risk factors that contribute to later metabolic dysfunction. These reproductive traits include the age at menarche, menstrual irregularity, the development of polycystic ovary syndrome, gestational weight change, gestational ...
Source: Cell Metabolism - January 27, 2024 Category: Cytology Authors: Amy R Nichols Jorge E Chavarro Emily Oken Source Type: research
Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB
Cell Metab. 2024 Jan 17:S1550-4131(24)00001-9. doi: 10.1016/j.cmet.2024.01.001. Online ahead of print.ABSTRACTThat uncoupling protein 1 (UCP1) is the sole mediator of adipocyte thermogenesis is a conventional viewpoint that has primarily been inferred from the attenuation of the thermogenic output of mice genetically lacking Ucp1 from birth (germline Ucp1-/-). However, germline Ucp1-/- mice harbor secondary changes within brown adipose tissue. To mitigate these potentially confounding ancillary changes, we constructed mice with inducible adipocyte-selective Ucp1 disruption. We find that, although germline Ucp1-/- mice succ...
Source: Cell Metabolism - January 25, 2024 Category: Cytology Authors: Janane F Rahbani Jakub Bunk Damien Lagarde Bozena Samborska Anna Roesler Haopeng Xiao Abhirup Shaw Zafir Kaiser Jessica L Braun Mia S Geromella Val A Fajardo Robert A Koza Lawrence Kazak Source Type: research
Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment
Cell Metab. 2024 Jan 17:S1550-4131(23)00477-1. doi: 10.1016/j.cmet.2023.12.026. Online ahead of print.ABSTRACTThe brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal Lactobacil...
Source: Cell Metabolism - January 24, 2024 Category: Cytology Authors: Wei Wei Yali Liu Yuanlong Hou Shuqi Cao Zhuo Chen Youying Zhang Xiaoying Cai Qingyuan Yan Ziguang Li Yonggui Yuan Guangji Wang Xiao Zheng Haiping Hao Source Type: research
Understanding the variation in exercise responses to guide personalized physical activity prescriptions
Cell Metab. 2024 Jan 17:S1550-4131(23)00476-X. doi: 10.1016/j.cmet.2023.12.025. Online ahead of print.ABSTRACTUnderstanding the factors that contribute to exercise response variation is the first step in achieving the goal of developing personalized exercise prescriptions. This review discusses the key molecular and other mechanistic factors, both extrinsic and intrinsic, that influence exercise responses and health outcomes. Extrinsic characteristics include the timing and dose of exercise, circadian rhythms, sleep habits, dietary interactions, and medication use, whereas intrinsic factors such as sex, age, hormonal statu...
Source: Cell Metabolism - January 23, 2024 Category: Cytology Authors: John Noone Justine M Mucinski James P DeLany Lauren M Sparks Bret H Goodpaster Source Type: research
Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating
Cell Metab. 2024 Feb 6;36(2):393-407.e7. doi: 10.1016/j.cmet.2023.12.014. Epub 2024 Jan 18.ABSTRACTFood is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of...
Source: Cell Metabolism - January 19, 2024 Category: Cytology Authors: Molly McDougle Alan de Araujo Arashdeep Singh Mingxin Yang Isadora Braga Vincent Paille Rebeca Mendez-Hernandez Macarena Vergara Lauren N Woodie Abhishek Gour Abhisheak Sharma Nikhil Urs Brandon Warren Guillaume de Lartigue Source Type: research
Lysine acetyltransferase 6A maintains CD4 < sup > + < /sup > T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity
Cell Metab. 2024 Jan 17:S1550-4131(23)00467-9. doi: 10.1016/j.cmet.2023.12.016. Online ahead of print.ABSTRACTAugmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, ...
Source: Cell Metabolism - January 18, 2024 Category: Cytology Authors: Jia-Yao Fu Shi-Jia Huang Bao-Li Wang Jun-Hao Yin Chang-Yu Chen Jia-Bao Xu Yan-Lin Chen Shuo Xu Ting Dong Hao-Nan Zhou Xin-Yi Ma Yi-Ping Pu Hui Li Xiu-Juan Yang Li-Song Xie Zhi-Jun Wang Qi Luo Yan-Xiong Shao Lei Ye Zi-Rui Zong Xin-Di Wei Wan-Wen Xiao Shu-T Source Type: research
Downregulation of the kidney glucagon receptor, essential for renal function and systemic homeostasis, contributes to chronic kidney disease
Cell Metab. 2024 Jan 11:S1550-4131(23)00475-8. doi: 10.1016/j.cmet.2023.12.024. Online ahead of print.ABSTRACTThe glucagon receptor (GCGR) in the kidney is expressed in nephron tubules. In humans and animal models with chronic kidney disease, renal GCGR expression is reduced. However, the role of kidney GCGR in normal renal function and in disease development has not been addressed. Here, we examined its role by analyzing mice with constitutive or conditional kidney-specific loss of the Gcgr. Adult renal Gcgr knockout mice exhibit metabolic dysregulation and a functional impairment of the kidneys. These mice exhibit hypera...
Source: Cell Metabolism - January 18, 2024 Category: Cytology Authors: May-Yun Wang Zhuzhen Zhang Shangang Zhao Toshiharu Onodera Xue-Nan Sun Qingzhang Zhu Chao Li Na Li Shiuhwei Chen Megan Paredes Laurent Gautron Maureen J Charron Denise K Marciano Ruth Gordillo Daniel J Drucker Philipp E Scherer Source Type: research
Augmentation of scleral glycolysis promotes myopia through histone lactylation
Cell Metab. 2024 Jan 9:S1550-4131(23)00474-6. doi: 10.1016/j.cmet.2023.12.023. Online ahead of print.ABSTRACTMyopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or ...
Source: Cell Metabolism - January 17, 2024 Category: Cytology Authors: Xiaolei Lin Yi Lei Miaozhen Pan Changxi Hu Bintao Xie Wenjing Wu Jianzhong Su Yating Li Yuhan Tan Xiaohuan Wei Zhengbo Xue Ruiyan Xu Mengqi Di Hanyu Deng Shengcong Liu Xingxing Yang Jia Qu Wei Chen Xiangtian Zhou Fei Zhao Source Type: research
Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity
Cell Metab. 2024 Jan 3:S1550-4131(23)00471-0. doi: 10.1016/j.cmet.2023.12.020. Online ahead of print.ABSTRACTThe roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have in...
Source: Cell Metabolism - January 17, 2024 Category: Cytology Authors: Zilong Zhang Xu Xu Di Zhang Songsong Zhao Chuyi Wang Guilin Zhang Wenshu Chen Jinglin Liu Huimin Gong Youlutuziayi Rixiati Shi Li Tong Shen Jianming Li Source Type: research
Niche-specific control of tissue function by regulatory T cells-Current challenges and perspectives for targeting metabolic disease
Cell Metab. 2024 Feb 6;36(2):229-239. doi: 10.1016/j.cmet.2023.12.019. Epub 2024 Jan 12.ABSTRACTTissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, and function. Accordingly, Tregs play a crucial role in controlling obesity-induced inflammation and supporting efficient muscle function and repair. Depending on the tissue context, Tregs are characterized by unique transcriptomes, growth, and survival factors and T cell receptor (TCR) repertoires. This functional specialization offers the potential to selectively target context-spe...
Source: Cell Metabolism - January 13, 2024 Category: Cytology Authors: Maike Becker Sandra M Dirschl Martin G Scherm Isabelle Serr Carolin Daniel Source Type: research
