The emerging role of FHL2 in metabolism

Type 2 diabetes mellitus (T2DM) and obesity are increasingly prevalent. Both multifactorial, metabolic diseases increase the risk of developing further health complications and are associated with aging. Four and a Half LIM domains 2 (FHL2) is highly expressed in specific tissues and its expression is known to increase with age. This led us to hypothesize regarding the role of FHL2 in age-related metabolic diseases.
We applied FHL2-deficient mice to evaluate the effect of this gene on glucose homeostasis, obesity, lipid profile, and vascular tone. The results revealed that lacking FHL2 improves glucose clearance and insulin secretion in mice due to improved function of the insulin-producing pancreatic beta-cells. In humans, FHL2 expression is increased in white adipose tissue of obese individuals, and FHL2-deficient mice were shown to be resistant to obesity. Moreover, deficiency for FHL2 causes increased energy expenditure due to so-called ‘browning’ of the white adipose tissue. In addition, through investigation of a large multi-ethnic cohort, we demonstrated that FHL2 genetic polymorphisms are associated with diabetogenic lipid profile parameters, but not with HbA1c or T2DM. This highlights the need for further research into FHL2 in humans. Lastly, we also demonstrated that perivascular adipose tissue (PVAT) isolated from FHL2-deficient mice improves vascular tone and vasodilation in microvascular resistance arteries.
In conclusion, these findings suggest that reduced FHL2 expression is beneficial in metabolic disorders, including obesity and T2DM, and improves vascular function.