Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk
Cell Metab. 2023 Nov 7;35(11):2028-2043.e7. doi: 10.1016/j.cmet.2023.10.013.ABSTRACTIdentification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Shixing Ma Xiaotao Xing Haisen Huang Xin Gao Xun Xu Jian Yang Chengcheng Liao Xuanhao Zhang Jinglun Liu Weidong Tian Li Liao Source Type: research

Bone marrow immune cells stop weight regain
Cell Metab. 2023 Nov 7;35(11):1845-1846. doi: 10.1016/j.cmet.2023.10.004.ABSTRACTWeight regain is a major challenge in the long-term management of obesity; however, the underlying mechanisms remain unclear. Zhou et al. found that bone-marrow-derived CD7+ monocytes respond to fluctuating nutritional stress and suppress weight regain by promoting beige fat thermogenesis.PMID:37939653 | DOI:10.1016/j.cmet.2023.10.004 (Source: Cell Metabolism)
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Jing Yan Cheng Hu Source Type: research

Colonic macrophages eat and feed
Cell Metab. 2023 Nov 7;35(11):1847-1848. doi: 10.1016/j.cmet.2023.10.006.ABSTRACTMacrophages not only secure host defense via phagocytosis but also play a key role in tissue homeostasis. A comprehensive study by Fritsch et al. reveals a novel mechanism by which macrophages in the colon deliver polyamines to epithelial cells to support self-renewal of the epithelium during periods of high proliferation.PMID:37939654 | DOI:10.1016/j.cmet.2023.10.006 (Source: Cell Metabolism)
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Jan Van den Bossche Source Type: research

Regenerating the heart by metabolically reprogramming the cardiomyocyte epigenome
Cell Metab. 2023 Nov 7;35(11):1849-1851. doi: 10.1016/j.cmet.2023.10.007.ABSTRACTIn mammal adolescence, cardiomyocytes rapidly exit the cell cycle, and heart regeneration in adults is limited after cardiac injury. Recent work by Li et al. in Nature revealed that inhibition of fatty acid oxidation can rewire cell metabolism and lead to epigenetic reprogramming of cardiomyocytes to an immature state that facilitates cardiomyocyte cell-cycle reentry and heart regeneration in adult animals.PMID:37939655 | DOI:10.1016/j.cmet.2023.10.007 (Source: Cell Metabolism)
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Xiaoqiang Tang Source Type: research

The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease
Cell Metab. 2023 Nov 7;35(11):1852-1871. doi: 10.1016/j.cmet.2023.10.009.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage liver diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms of the immune system or their unidirectional interplay are commonly studied in MASLD. However, the bidirectional communication between innate and adaptive immune systems and its impact on MASLD remain insufficiently understood. Given that both innate and ada...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Keisuke Sawada Hak Chung Samir Softic Maria E Moreno-Fernandez Senad Divanovic Source Type: research

Mitohormesis
Cell Metab. 2023 Nov 7;35(11):1872-1886. doi: 10.1016/j.cmet.2023.10.011.ABSTRACTPerturbation of mitochondrial function can trigger a host of cellular responses that seek to restore cellular metabolism, cytosolic proteostasis, and redox homeostasis. In some cases, these responses persist even after the stress is relieved, leaving the cell or tissue in a less vulnerable state. This process-termed mitohormesis-is increasingly viewed as an important aspect of normal physiology and a critical modulator of various disease processes. Here, we review aspects of mitochondrial stress signaling that, among other things, can rewire t...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Yu-Wei Cheng Jie Liu Toren Finkel Source Type: research

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice
Cell Metab. 2023 Nov 7;35(11):1976-1995.e6. doi: 10.1016/j.cmet.2023.10.005.ABSTRACTLow-protein diets promote health and longevity in diverse species. Restriction of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine recapitulates many of these benefits in young C57BL/6J mice. Restriction of dietary isoleucine (IleR) is sufficient to promote metabolic health and is required for many benefits of a low-protein diet in C57BL/6J males. Here, we test the hypothesis that IleR will promote healthy aging in genetically heterogeneous adult UM-HET3 mice. We find that IleR improves metabolic health in young and ol...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Cara L Green Michaela E Trautman Krittisak Chaiyakul Raghav Jain Yasmine H Alam Reji Babygirija Heidi H Pak Michelle M Sonsalla Mariah F Calubag Chung-Yang Yeh Anneliese Bleicher Grace Novak Teresa T Liu Sarah Newman Will A Ricke Kristina A Matkowskyj Ire Source Type: research

Impact of biological sex and sex hormones on molecular signatures of skeletal muscle at rest and in response to distinct exercise training modes
Cell Metab. 2023 Nov 7;35(11):1996-2010.e6. doi: 10.1016/j.cmet.2023.10.010.ABSTRACTSubstantial divergence in cardio-metabolic risk, muscle size, and performance exists between men and women. Considering the pivotal role of skeletal muscle in human physiology, we investigated and found, based on RNA sequencing (RNA-seq), that differences in the muscle transcriptome between men and women are largely related to testosterone and estradiol and much less related to genes located on the Y chromosome. We demonstrate inherent unique, sex-dependent differences in muscle transcriptional responses to aerobic, resistance, and combined...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Mark W Pataky Surendra Dasari Kelly L Michie Kyle J Sevits A Aneesh Kumar Katherine A Klaus Carrie J Heppelmann Matthew M Robinson Rickey E Carter Ian R Lanza K Sreekumaran Nair Source Type: research

Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk
Cell Metab. 2023 Nov 7;35(11):2028-2043.e7. doi: 10.1016/j.cmet.2023.10.013.ABSTRACTIdentification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in...
Source: Cell Metabolism - November 8, 2023 Category: Cytology Authors: Shixing Ma Xiaotao Xing Haisen Huang Xin Gao Xun Xu Jian Yang Chengcheng Liao Xuanhao Zhang Jinglun Liu Weidong Tian Li Liao Source Type: research

The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Cell Metab. 2023 Nov 7;35(11):1887-1896.e5. doi: 10.1016/j.cmet.2023.10.008. Epub 2023 Oct 30.ABSTRACTThe PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty acids we...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Panu K Luukkonen Kimmo Porthan Noora Ahlholm Fredrik Rosqvist Sylvie Dufour Xian-Man Zhang Tiina E Lehtim äki Wenla Sepp änen Marju Orho-Melander Leanne Hodson Kitt Falk Petersen Gerald I Shulman Hannele Yki-J ärvinen Source Type: research

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research

The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Cell Metab. 2023 Oct 20:S1550-4131(23)00377-7. doi: 10.1016/j.cmet.2023.10.008. Online ahead of print.ABSTRACTThe PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty ...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Panu K Luukkonen Kimmo Porthan Noora Ahlholm Fredrik Rosqvist Sylvie Dufour Xian-Man Zhang Tiina E Lehtim äki Wenla Sepp änen Marju Orho-Melander Leanne Hodson Kitt Falk Petersen Gerald I Shulman Hannele Yki-J ärvinen Source Type: research

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research

The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Cell Metab. 2023 Oct 20:S1550-4131(23)00377-7. doi: 10.1016/j.cmet.2023.10.008. Online ahead of print.ABSTRACTThe PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty ...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Panu K Luukkonen Kimmo Porthan Noora Ahlholm Fredrik Rosqvist Sylvie Dufour Xian-Man Zhang Tiina E Lehtim äki Wenla Sepp änen Marju Orho-Melander Leanne Hodson Kitt Falk Petersen Gerald I Shulman Hannele Yki-J ärvinen Source Type: research

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research