A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism
Herman MA, Peroni OD, Villoria J, Schön MR, Abumrad NA, Blüher M, Klein S, Kahn BB
Nature. 2012 Apr 19;484(7394):333-8. PMID: 22466288
Loss of ChREBP in adipocytes of mice causes insulin resistance in liver, muscle, and fat
Adipocytes lacking ChREBP have defects in glucose transport and Glut4 translocation
ChREBP deletion in fat lowers abundance of palmitic acid hydroxy stearic acids (PAHSAs)
PAHSAs reverse insulin resistance and glucose transport defects with ChREBP loss in fat
Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport
Vijayakumar A, Aryal P, Wen J, Syed I, Vazirani RP, Moraes-Vieira PM, Camporez JP, Gallop MR, Perry RJ, Peroni OD, Shulman GI, Saghatelian A, McGraw TE, Kahn BB
Cell Rep. 2017 Oct 24;21(4):1021-1035. PMID: 29069585
Loss of ChREBP in adipocytes of mice causes insulin resistance in liver, muscle, and fat
Adipocytes lacking ChREBP have defects in glucose transport and Glut4 translocation
ChREBP deletion in fat lowers abundance of palmitic acid hydroxy stearic acids (PAHSAs)
PAHSAs reverse insulin resistance and glucose transport defects with ChREBP loss in fat
Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects
Yore MM, Syed I, Moraes-Vieira PM, Zhang T, Herman MA, Homan EA, Patel RT, Lee J, Chen S, Peroni OD, Dhaneshwar AS, Hammarstedt A, Smith U, McGraw TE, Saghatelian A, Kahn BB
Cell. 2014 Oct 09; 159(2):318-32. PMID: 25303528
Lipidomics identifies bioactive fatty acid esters of hydroxyl-fatty acids (FAHFAs)
FAHFAs are low in insulin-resistant humans and correlate with insulin sensitivity
These lipids improve insulin secretion and glucose tolerance in mice
FAHFAs block inflammatory cytokine production and reduce adipose inflammation
Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis
Syed I, Lee J, Moraes-Vieira PM, Donaldson CJ, Sontheimer A, Aryal P, Wellenstein K, Kolar MJ, Nelson AT, Siegel D, Mokrosinski J, Farooqi IS, Zhao JJ, Yore MM, Peroni OD, Saghatelian A, Kahn BB
Cell Metab. 2018 Feb 6;27(2):419-427.e4. PMID: 29414687
Chronic PAHSA treatment improves insulin sensitivity in chow- and HFD-fed mice
PAHSAs activate GPR40, which mediates their augmentation of insulin secretion
GPR40 plays a role in the beneficial effects of PAHSAs on glucose homeostasis
GLP-1 receptor indirectly mediates PAHSA effects on glucose tolerance
PAHSAs attenuate immune responses and promote β cell survival in autoimmune diabetic mice
Syed I, Rubin de Celis MF, Mohan JF, Moraes-Vieira PM, Vijayakumar A, Nelson AT, Siegel D, Saghatelian A, Mathis D, Kahn BB
J Clin Invest. 2019 Aug 5;129(9):3717-3731. PMID: 31380811
PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms
Zhou P, Santoro A, Peroni OD, Nelson AT, Saghatelian A, Siegel D, Kahn BB
J Clin Invest. 2019 Oct 01; 129(10):4138-4150. PMID: 31449056
Retinol binding protein 4 primes the NLRP3 inflammasome by signaling through Toll-like receptors 2 and 4
Moraes-Vieira PM, Yore MM, Sontheimer-Phelps A, Castoldi A, Norseen J, Aryal P, Sjödin KS, Kahn BB
Proc Natl Acad Sci USA. 2020 Dec 8;117(49):31309-31318. PMID: 33214151
Insulin action in adipocytes, adipose remodeling, and systemic effects
Santoro A, McGraw TE, Kahn BB
Cell Metab. 2021 Apr 06; 33(4):748-757. PMID: 33826917
BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis
Lee J, Vijayakumar A, White PJ, Xu Y, Ilkayeva O, Lynch CJ, Newgard CB, Kahn BB
Endocrinology. 2021 Jul 1; 162(7):bqab062. PMID: 33765118
ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty acids
Patel R, Santoro A, Hofer P, Tan D, Oberer M, Nelson AT, Konduri S, Siegel D, Zechner R, Saghatelian A, Kahn BB
Nature. 2022 Jun 08; 1606(7916):968-975. PMID: 35676490
PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53
Rubin de Celis MF, Garcia-Martin R, Syed I, Lee J, Aguayo-Mazzucato C, Bonner-Weir S, Kahn BB
Proc Natl Acad Sci U S A. 2022 Nov 22;119(47):e2206923119. PMID: 36375063
Adipocyte Regulation of Insulin Sensitivity and the Risk of Type 2 Diabetes
Santoro A, Kahn BB
N Engl J Med. 2023 Jun 1;388(22):2071-85. PMID: 37256977
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