Interorgan Metabolic Crosstalk in Human Insulin Resistance

Physiological Reviews
Sofiya GanchevaMichael Roden

Abstract

Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism. Circulating lipids such as free fatty acids, acetate, and palmitoleate from adipose tissue and short-chain fatty acids from the gut effectively act on liver and skeletal muscle. Intracellular lipids such as diacylglycerols and sphingolipids can serve as lipotoxins by directly inhibiting insulin action in muscle and liver. In contrast, fatty acid esters of hydroxy fatty acids have been recently shown to exert a series of beneficial effects. Also, ketoacids are gaining interest as potent modulators of insulin action and mitochondrial function. Finally, branched-chain amino acids not only predict metabolic diseases, but also inhibit insulin signaling. Here, we focus on the metabolic crosst...Continue Reading

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Citations

Aug 15, 2018·European Journal of Clinical Investigation·Kálmán Bódis, Michael Roden
Jun 27, 2018·American Journal of Physiology. Endocrinology and Metabolism·Yoshinao KobayashiOsamu Taguchi
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Sep 24, 2019·The Journal of Clinical Investigation·Theresia Sarabhai, Michael Roden
Dec 12, 2019·Alimentary Pharmacology & Therapeutics·Noemí CabréJorge Joven
Dec 12, 2019·The Journal of Biological Chemistry·Marie-Christine SimonMichael Roden
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Sep 15, 2019·Nature Communications·Sofiya GanchevaMichael Roden
Mar 3, 2020·Journal of Inherited Metabolic Disease·Sofiya GanchevaRegina Ensenauer
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Nov 22, 2020·BMJ Open Diabetes Research & Care·Maria ApostolopoulouMichael Roden
Oct 24, 2020·Nature Reviews. Gastroenterology & Hepatology·Sven FrancqueFrank Tacke
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Methods Mentioned

BETA
biopsies
biopsy

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