title: αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.
abstract: Emerging evidence suggests molecular chaperones have a role in the pathogenesis of obesity and diabetes. As αB-crystallin and HspB2 are molecular chaperones and data suggests their expression is elevated in the skeletal muscle of diabetic and obese animals, we sought to determine if αB-crystallin and HspB2 collectively play a functional role in the metabolic phenotype of diet-induced obesity. Using αB-crystallin/HspB2 knockout and littermate wild-type controls, it was observed that mice on the high fat diet gained more weight as compared to the normal chow group and genotype did not impact this weight gain. To test if the genotype and/or diet influenced glucose homeostasis, intraperitoneal glucose challenge was performed. While similar on normal chow diet, wild-type mice on the high fat diet exhibited higher glucose levels during the glucose challenge compared to the αB-crystallin/HspB2 knockout mice. Although wild-type mice had higher glucose levels, insulin levels were similar for both genotypes. Insulin tolerance testing revealed that αB-crystallin/HspB2 knockout mice were more sensitive to insulin, leading to lower glucose levels over time, which is indicative of a difference in insulin sensitivity between the genotypes on a high fat diet. Transcriptome analyses of skeletal muscle in αB-crystallin/HspB2 knockout and wild-type mice on a normal or high fat diet revealed reductions in cytokine pathway genes in αB-crystallin/HspB2 knockout mice, which may contribute to their improved insulin sensitivity. Collectively, these data reveal that αB-crystallin/HspB2 plays a role in development of insulin resistance during a high fat diet challenge.
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Toft
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Miles
authors.initials: M
authors.lastname: Fuller
authors.affiliation: Next Generation Sequencing Core, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schipma
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Cryns
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United States.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Layden
keywords: Glucose tolerance; HspB2; αB-crystallin