Life Metabolism

VOLUME 2 | ISSUE 1 | Feb 2023

The image shows that different foods influence the depressive behaviors of mice. Feixiang Yuan et al. discovered that leucine-deficient diet has antidepressant effects on chronic restraint stress-induced depression-related behaviors, mediated by activation of GCN2 in hypothalamic AgRP neurons. These results suggest that metabolism-related neurons could sense nutrient levels and thereby regulate behaviors.


RESEARCH HIGHLIGHTS

Jessie C Morrill, Qingchun Tong · 08 Feb 2023 load006

In a recent paper published in Life Metabolism, Yuan et al. demonstrated that deprivation of the essential amino acid, leucine, alleviated depressive behaviors that were induced by chronic stress. Specifically, the antidepressant effects were shown to be mediated by the activation of agouti-related protein (AgRP)-expressing neurons, which are known for the ability to sense bodily energy status and promote energy intake, revealing a neural basis for the availability of nutrients in controlling mental behaviors.

Juan Wang, Guosheng Liang, Tong-Jin Zhao · 12 Aug 2022 loac016

In a recent article published in Nature, Patel et al. identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2) as the first biosynthetic enzyme of fatty acid esters of hydroxy fatty acids (FAHFAs), further expanding the knowledge on bioactive lipid research and being a potential paradigm shift for ATGL studies.

Guang Lu, Han-Ming Shen · 19 Oct 2022 loac029

CLN3 is a lysosomal transmembrane protein and loss of CLN3 is known to cause a juvenile lethal neurodegenerative lysosomal storage disorder (LSD), called Batten disease. In a recent study published in Nature, Laqtom et al. reported a novel function of CLN3 in the clearance of glycerophospholipid from lysosomes via lysosomal efflux of glycerophosphodiesters (GPDs), not only establishing a deeper mechanistic understanding of Batten disease, but also suggesting both the diagnostic and therapeutic potential of CLN3-GPDs in this type of neurodegenerative LSD.

Wei Jia, Xiaojiao Zheng · 17 Nov 2022 loac033

Cigarette smoking is considered a risk factor for nonalcoholic fatty liver disease (NAFLD). In a study recently published in Nature, Chen et al. unveiled a mechanistic role of nicotine in NAFLD progression. In addition, they identified a gut bacterium Bacteroides xylanisolvens that can reduce intestinal nicotine levels, and thus improve nicotine-induced NAFLD phenotypes in mice.

PERSPECTIVE

Xuelian Xiong, Xiaoying Li · 21 Feb 2023 load007

Both non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are highly prevalent metabolic liver diseases. Accumulating epidemiological evidence now indicates that NAFLD and T2DM are strongly associated, yet the causative relationship remains to be elucidated. Liver serves as a hub for nutrient and energy metabolism in the body. Here we demonstrated the pathogenesis linking NAFLD to T2DM through a series of studies and the attenuation of T2DM progression after NALFD improvement in cohort study. We proposed the urgent necessity of NAFLD management and NAFLD drug development, which might be novel therapeutic avenues for T2DM.

REVIEW ARTICLES

Hanlin Zhang, Xinyu Li, Wudi Fan, Sentibel Pandovski, Ye Tian · 07 Jan 2023 load001

Mitochondria function as a hub of the cellular metabolic network. Mitochondrial stress is closely associated with aging and a variety of diseases, including neurodegeneration and cancer. Cells autonomously elicit specific stress responses to cope with mitochondrial stress to maintain mitochondrial homeostasis. Interestingly, mitochondrial stress responses may also be induced in a non-autonomous manner in cells or tissues that are not directly experiencing such stress. Such non-autonomous mitochondrial stress responses are mediated by secreted molecules called mitokines. Due to their significant translational potential in improving human metabolic health, there has been a surge in mitokine-focused research. In this review, we summarize the findings regarding inter-tissue communication of mitochondrial stress in animal models. In addition, we discuss the possibility of mitokine-mediated intercellular mitochondrial communication originating from bacterial quorum sensing.

Min Peng, Ming O Li · 19 Jan 2023 load002

T cells are one of few cell types in adult mammals that can proliferate extensively and differentiate diversely upon stimulation, which serves as an excellent example to dissect the metabolic basis of cell fate decisions. During the last decade, there has been an explosion of research into the metabolic control of T cell responses. The roles of common metabolic pathways, including glycolysis, lipid metabolism and mitochondrial oxidative phosphorylation, in T cell responses have been well-characterized, and their mechanisms of action are starting to emerge. In this Review, we present several considerations for T cell metabolism-focused research, while providing an overview of the metabolic control of T cell fate decisions during their life journey. We try to synthesize principles that explain the causal relationship between cellular metabolism and T cell fate decision. We also discuss key unresolved questions and challenges in targeting T cell metabolism to treat disease.

ORIGINAL ARTICLES

Feixiang Yuan, Shangming Wu, Ziheng Zhou, Fuxin Jiao, Hanrui Yin · 04 Feb 2023 load004