Feeding Diversified Protein Sources Exacerbates Hepatic Insulin Resistance via Increased Gut Microbial Branched-Chain Fatty Acids and mTORC1 Signaling in Obese Mice

Scientists showed that the branched-chain fatty acids, isobutyric and isovaleric acid, increased glucose production and activated mTORC1/S6K1 in hepatocytes.
[Nature Communications]
Choi, B. S.-Y., Daniel, N., Houde, V. P., Ouellette, A., Marcotte, B., Varin, T. V., Vors, C., Feutry, P., Ilkayeva, O., Ståhlman, M., St-Pierre, P., Bäckhed, F., Tremblay, A., White, P. J., & Marette, A. (2021). Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice. Nature Communications, 12(1), 3377. https://doi.org/10.1038/s41467-021-23782-w Cite
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Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis

Researchers explored whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. In vitro models of the normal breast epithelium showed that lipopolysaccharide disrupted tight junctions and compromised epithelial permeability.
[Cancer Research]
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High-Fat Diet-Activated Fatty Acid Oxidation Mediates Intestinal Stemness and Tumorigenicity

Scientists proposed that a high-fat diet enhanced intestinal stemness and tumorigenicity by engaging a peroxisome proliferator-activated receptor-fatty acid oxidation (PPAR-FAO) program.
[Cell Reports]
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Visceral Obesity and Insulin Resistance Associate with CD36 Deletion in Lymphatic Endothelial Cells

Investigators showed that that intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries to collecting vessels, and that LEC CD36 regulated lymphatic integrity and optimized lipid transport.
[Nature Communications]
Cifarelli, V., Appak-Baskoy, S., Peche, V. S., Kluzak, A., Shew, T., Narendran, R., Pietka, K. M., Cella, M., Walls, C. W., Czepielewski, R., Ivanov, S., Randolph, G. J., Augustin, H. G., & Abumrad, N. A. (2021). Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells. Nature Communications, 12(1), 3350. https://doi.org/10.1038/s41467-021-23808-3 Cite
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Type 2 Diabetes Mellitus Duration and Obesity Alter the Efficacy of Autologously Transplanted Bone Marrow-Derived Mesenchymal Stem/Stromal Cells

Investigators tested the hypothesis that autologous bone-marrow mesenchymal stem cell (BM-MSC) administration in type 2 diabetes patient was safe and that the efficacy of the treatment was dependant on the quality of the autologous BM-MSC population and administration routes.
[Stem Cells Translational Medicine]
Nguyen, L. T., Hoang, D. M., Nguyen, K. T., Bui, D. M., Nguyen, H. T., Le, H. T. A., Hoang, V. T., Bui, H. T. H., Dam, P. T. M., Hoang, X. T. A., Ngo, A. T. L., Le, H. M., Phung, N. Y., Vu, D. M., Duong, T. T., Nguyen, T. D., Ha, L. T., Bui, H. T. P., Nguyen, H. K., … Bui, A. V. (n.d.). Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/https://doi.org/10.1002/sctm.20-0506 Cite
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LncRNA H19 Governs Mitophagy and Restores Mitochondrial Respiration in the Heart through Pink1/Parkin Signaling during Obesity

The effects of long non-coding RNA H19 (H19) on metabolic disorders, mitochondrial respiratory function, and mitophagy were investigated. Researchers suggested that DNA methylation-mediated downregulation of H19 expression played a crucial role in cardiomyocyte metabolic disorders.
[Cell Death & Disease]
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Gut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF-1 Signaling

Oral administration of an antibiotic mixture in prostate cancer (PCa)-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited PCa cell proliferation, and reduced prostate Igf1 expression and circulating IGF-1 levels.
[Cancer Research]
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Orphan GPR116 Mediates the Insulin Sensitizing Effects of the Hepatokine FNDC4 in Adipose Tissue

Scientists found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice.
[Nature Communications]
Georgiadi, A., Lopez-Salazar, V., Merahbi, R. E.-, Karikari, R. A., Ma, X., Mourão, A., Klepac, K., Bühler, L., Alfaro, A. J., Kaczmarek, I., Linford, A., Bosma, M., Shilkova, O., Ritvos, O., Nakamura, N., Hirose, S., Lassi, M., Teperino, R., Machado, J., … Herzig, S. (2021). Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue. Nature Communications, 12(1), 2999. https://doi.org/10.1038/s41467-021-22579-1 Cite
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UCP1 Governs Liver Extracellular Succinate and Inflammatory Pathogenesis

Researchers identified an endocrine pathway regulated by Uncoupling protein 1 (UCP1) that antagonizes liver inflammation and pathology, independent of effects on obesity.
[Nature Metabolism]
Mills, E. L., Harmon, C., Jedrychowski, M. P., Xiao, H., Garrity, R., Tran, N. V., Bradshaw, G. A., Fu, A., Szpyt, J., Reddy, A., Prendeville, H., Danial, N. N., Gygi, S. P., Lynch, L., & Chouchani, E. T. (2021). UCP1 governs liver extracellular succinate and inflammatory pathogenesis. Nature Metabolism, 1–14. https://doi.org/10.1038/s42255-021-00389-5 Cite
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Non-alcoholic Fatty Liver Disease in Obese Children and Adolescents: A Role for Nutrition?

Diet composition and in particular simple carbohydrate intake may promote the development of Non-alcoholic fatty liver disease, whereas non-digestible carbohydrates (dietary fiber), by affecting gut microbiota, may favour the integrity of gut wall and reduce inflammation, opposing this process.
[European Journal of Clinical Nutrition]
Bonsembiante, L., Targher, G., & Maffeis, C. (2021). Non-alcoholic fatty liver disease in obese children and adolescents: a role for nutrition? European Journal of Clinical Nutrition, 1–12. https://doi.org/10.1038/s41430-021-00928-z Cite
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Endocrine Role of Bone in the Regulation of Energy Metabolism

The authors summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
[Bone Research]
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