Brown adipose tissue prevents glucose intolerance and cardiac remodeling in high-fat-fed mice after a mild myocardial infarction

Abstract

Background Obesity increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes (T2D) after myocardial infarction (MI). Brown adipose tissue (BAT) is important to combat obesity and T2D, and increasing BAT mass by transplantation improves glucose metabolism and cardiac function. The objective of this study was to determine if BAT had a protective effect on glucose tolerance and cardiac function in high-fat diet (HFD) fed mice subjected to a mild MI. Methods Male C57BL/6 mice were fed a HFD for eight weeks and then divided into Sham (Sham-operated) and +BAT (mice receiving 0.1 g BAT into their visceral cavity). Sixteen weeks post-transplantation, mice were further subdivided into ±MI (Sham; Sham-MI; +BAT; +BAT-MI) and maintained on a HFD. Cardiac (echocardiography) and metabolic function (glucose and insulin tolerance tests, body composition and exercise tolerance) were assessed throughout 22 weeks post-MI. Quantitative PCR (qPCR) was performed to determine the expression of genes related to metabolic function of perigonadal adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), liver, heart, tibialis anterior skeletal muscle (TA); and BAT. Results +BAT prevented the increase in left ventricle mass (LVM) and exercise intolerance in response to MI. Similar to what is observed in humans, Sham-MI mice developed IGT post-MI, but this was negated in +BAT-MI mice. IGT was independent of changes in body composition. Genes involved in inflammation, insulin resistance, and metabolism were significantly altered in pgWAT, scWAT, and liver in Sham-MI mice compared to all other groups. Conclusions BAT transplantation prevents IGT, the increase in LVM, and exercise intolerance following MI. MI alters the expression of several metabolic-related genes in WAT and liver in Sham-MI mice, suggesting that these tissues may contribute to the impaired metabolic response. Increasing BAT may be an important intervention to prevent the development of IGT or T2D and cardiac remodeling in obese patients post-MI.

UCP1‐dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress

“…Accumulating preclinical evidence suggests an inverse relationship between BAT activity and pathological cardiac hypertrophy and HF. [16][17][18][19][20][21][22] This is further supported by recent clinical observations showing individuals with active BAT have lower risk of adverse cardiac events and decreased prevalence of HF. 5,11 However, the effect of BAT on the initial responses of hypertrophic signaling and cardiac metabolic remodeling during the induction of pathological stress has not been previously addressed.…”

Cardiometabolic Changes in Sirtuin1-Heterozygous Mice on High-Fat Diet and Melatonin Supplementation

“…However, in male mice, the epididymal WAT (eWAT) is the unique depot prone to inflammation and obesogenic remodeling [10,11]. The interscapular AT depot, called brown AT (iBAT), is fundamental for combating obesity and diabetes, favoring cardiac remodeling after mild infarction in mice [12]. The main histological fingerprint of pro-inflammatory changes in AT depots is the crown-like structure (CLS), a peculiar arrangement of infiltrating macrophages around dying adipocytes [13].…”

Brown fat holds promise for addressing obesity and a host of related ills

“…Beyond fighting obesity writ large, one could envision specific uses for brown fat—for example, as an infusion that protects heart attack victims from frequent after-effects that include developing type 2 diabetes or impaired heart functioning. A 2021 study found that mice fed a high-fat diet and then induced to have a heart attack had a better ability to process glucose and to exercise strenuously if they had received a prophylactic brown fat infusion soon after the heart attack ( 4 ). What’s more, compared with control mice, those who had received brown fat did not experience a common warning sign of coronary artery disease: an increase in the mass of the heart’s left ventricle.…”