Multiple effects of cold exposure on livers of male mice

Abstract

Cold exposure of mice is a common method to stimulate brown adipose tissue (BAT) activity and induce browning of white adipose tissue (WAT) that has beneficial effects on whole-body lipid metabolism, including reduced plasma triglyceride (TG) concentrations. The liver is a key regulatory organ in lipid metabolism as it can take up as well as oxidize fatty acids. The liver can also synthesize, store and secrete TGs in VLDL particles. The effects of cold exposure on murine hepatic lipid metabolism have not been addressed. Here, we report the effects of 24-h exposure to 4°C on parameters of hepatic lipid metabolism of male C57BL/6J mice. Cold exposure increased hepatic TG concentrations by 2-fold ( < 0.05) but reduced hepatic lipogenic gene expression. Hepatic expression of genes encoding proteins involved in cholesterol synthesis and uptake such as the LDL receptor (LDLR) was significantly increased upon cold exposure. Hepatic expression of encoding the rate-limiting enzyme in the classical bile acid (BA) synthesis pathway was increased by 4.3-fold ( < 0.05). Hepatic BA concentrations and fecal BA excretion were increased by 2.8- and 1.3-fold, respectively ( < 0.05 for both). VLDL-TG secretion was reduced by approximately 50% after 24 h of cold exposure ( < 0.05). In conclusion, cold exposure has various, likely intertwined effects on the liver that should be taken into account when studying the effects of cold exposure on whole-body metabolism.

Mild Hypothermia Attenuates Hepatic Ischemia–Reperfusion Injury through Regulating the JAK2/STAT3-CPT1a-Dependent Fatty Acid β-Oxidation

“…As is well known, hypothermia could lead to a significant reduction in body metabolism; cellular oxygen and glucose requirements decrease by an average of 5-8% for every degree of decrease in temperature [7,16,17]. However, the effects of the decrease in temperature on hepatic lipid metabolism are complex and interconnected [18][19][20][21]. Cold exposure increases hepatic triglyceride (TG) concentrations but reduces hepatic lipogenic gene expression [18].…”

“…However, the effects of the decrease in temperature on hepatic lipid metabolism are complex and interconnected [18][19][20][21]. Cold exposure increases hepatic triglyceride (TG) concentrations but reduces hepatic lipogenic gene expression [18]. Hepatic expression of genes encoding proteins involved in cholesterol synthesis and uptake and classical bile acid (BA) synthesis is significantly increased upon cold exposure [18,21].…”

“…Cold exposure increases hepatic triglyceride (TG) concentrations but reduces hepatic lipogenic gene expression [18]. Hepatic expression of genes encoding proteins involved in cholesterol synthesis and uptake and classical bile acid (BA) synthesis is significantly increased upon cold exposure [18,21]. After cold exposure, hepatic BA concentrations and fecal BA excretion are increased, while very low-density lipoprotein-(VLDL-) TG secretion is reduced [18,21].…”

“…Hepatic expression of genes encoding proteins involved in cholesterol synthesis and uptake and classical bile acid (BA) synthesis is significantly increased upon cold exposure [18,21]. After cold exposure, hepatic BA concentrations and fecal BA excretion are increased, while very low-density lipoprotein-(VLDL-) TG secretion is reduced [18,21]. Thus, it is very important to clarify whether the complex effects of hypothermia on hepatic lipid metabolism are involved in hepatic IR injury.…”

“…The liver is a key regulatory organ in lipid metabolism; it can take up as well as oxidize fatty acids; it can synthesize, store, and secrete TG in VLDL particles; and it is the main metabolic orsgan that controls whole-body cholesterol and BA metabolism [18,22]. More importantly, mitochondrial fatty acid β-oxidation (FAO) in the liver is the primary pathway for the oxidation of fatty acids and also the key metabolic pathway for energy homeostasis [23,24].…”