Adipose tissue μ-crystallin is a thyroid hormone-binding protein associated with systemic insulin sensitivity

Circulating thyroid hormones have been described to be intrinsically associated with insulin sensitivity in healthy subjects. μ-Crystallin is a nicotinamide adenine dinucleotide phosphate-dependent thyroid hormone-binding protein that has been shown to bind T3 in the cytoplasm. We aimed to study μ-Crystallin expression in adipose tissue and in muscle in association with insulin action and thyroid function.

μ-Crystallin gene expression was studied in 81 visceral and 75 sc adipose tissue samples and in 26 muscle samples from a cohort of subjects with a wide spectrum of adiposity (cohort 1). μ-Crystallin was also evaluated in 30 morbidly obese subjects in whom insulin action was evaluated using euglycemic clamp (cohort 2) and in 22 sc adipose tissue samples obtained before and after bariatric surgery-induced weight loss (cohort 3). μ-Crystallin was also evaluated during differentiation of human adipocytes. μ-Crystallin was overexpressed in human sc adipocytes using lentiviruses.

μ-Crystallin gene expression was 2.6- to 3-fold higher in sc vs visceral adipose tissue in direct association with the expression of thyroid hormone receptor α 1 in cohort 1 and cohort 2. Visceral, but not sc, adipose tissue μ-Crystallin was positively associated with the serum T3/T4 ratio in cohort 1 and with insulin sensitivity in cohort 2. In fact, μ-Crystallin gene expression was significantly decreased in visceral adipose tissue (-43%) and in muscle (-26%) in subjects with impaired fasting glucose and type 2 diabetes. Weight loss did not result in significant sc adipose tissue μ-Crystallin changes. μ-Crystallin overexpression led to increased insulin-induced (Ser473)Akt phosphorylation in sc adipocytes. During differentiation of adipocytes, μ-Crystallin gene expression decreased in both visceral (P = .006) and sc (P = .003) adipocytes from obese subjects.

Visceral, but not sc, adipose tissue μ-Crystallin is an adipose tissue factor linked to parameters of thyroid hormone action (T3/T4 ratio) and might mediate the interaction of thyroid function and insulin sensitivity.