Circadian rhythm disruption aggravated fat wasting in a rat model of heart failure-induced cachexia by increasing lipolysis, preventing lipid storage, and promoting brown adipocyte thermogenesis.
Does circadian rhythm misalignment aggravate adipose tissue depletion in heart failure-induced cachexia in a rat model?
Circadian rhythm disruption exacerbates adipose tissue wasting in heart failure-induced cachexia by promoting lipolysis and brown adipocyte thermogenesis.
p-value: p=<0.01
Abstract Background The circadian clock is involved in lipid metabolism in adipocytes. The impairment of circadian clocks is a major cause of metabolic diseases, but the pathophysiological role of the circadian clock in adipose tissue depletion, in cachexia, remains unclear. To address this issue, we investigated the effects of circadian clock misalignment on adipose tissue metabolism in cardiac cachexia. Methods We produced cardiac cachexia rat models through injection of monocrotaline (MCT), which caused pulmonary hypertension-induced heart failure (HF). Cardiac function was measured by echocardiography. The histological features in fat and liver tissue were observed by H moreover, smaller adipocytes and reduced lipid contents as well as increased extracellular matrix were found. In WAT, rats in the LD group exhibited elevated PKA-mediated lipolysis and WAT browning, while lipid storage was decreased as lipogenesis was inhibited. Meanwhile, in BAT, PKA-mediated thermogenesis was increased. NT-proBNP levels in blood and NE and IL-6 contents in adipose tissue were higher in the LD group than in the control group. Remarkably, compared with rats in the LD group, rats with circadian misalignment in the DL group and LV-Bmal1 shRNA group exhibited aggravated lipolysis and WAT browning, inhibited lipid storage in WAT, and elevated PKA-mediated thermogenesis in BAT. Moreover, rats in the DL group and LV-Bmal1 shRNA group showed higher levels of NT-proBNP in blood and NE and IL-6 contents in adipose tissue than rats in the LD group. Conclusion Our study suggested that a disrupted circadian rhythm aggravated fat wasting in patients with HF-induced cachexia by increasing lipolysis, preventing lipid storage in WAT and promoting beiging/brown adipocyte thermogenesis. This result indicated that stabilizing adipose tissue rhythms may help to combat disrupted energy homeostasis and alleviate excessive adipose tissue expenditure in HF-induced cachexia.
Ma et al. (Wed,) conducted a other in Heart failure-induced cachexia (n=50). Circadian rhythm disruption (altered light-dark cycle or Bmal1 knockdown) vs. Normal light:dark 12 h:12 h cycle or LV-Control shRNA was evaluated on Adipose tissue mass and markers of lipolysis and thermogenesis (p=<0.01). Circadian rhythm disruption aggravated fat wasting in a rat model of heart failure-induced cachexia by increasing lipolysis, preventing lipid storage, and promoting brown adipocyte thermogenesis.