Comparative proteomic study of liver lipid droplets and mitochondria in mice housed at different temperatures

Abstract

Laboratory mice are standardly housed at around 23 °C, setting them under chronic cold stress. Metabolic changes in the liver in mice housed at thermoneutral, standard and cold temperatures remain unknown. In the present study, we isolated lipid droplets and mitochondria from their livers in a comparative proteomic study aiming to investigate the changes. According to proteomic analysis, mitochondrial tricarboxylic acid cycle (TCA cycle) and retinol metabolism are enhanced, whereas oxidative phosphorylation is not affected obviously under cold conditions, suggesting that liver mitochondria may increase TCA cycle capacity in biosynthetic pathways, as well as retinol metabolism, to help the liver to adapt. Based on proteomic and immunoblotting results, perilipin 5 and major urinary proteins are increased significantly, whereas mitochondrial pyruvate carrier is decreased dramatically under cold conditions, indicating their involvement in liver adaptation.

Mitochondrial aconitase controls adipogenesis through mediation of cellular ATP production

“…We then studied the effect of temperature on the expression of Aco2. The result showed significantly higher levels of Aco2 mRNA and activity in iWAT of mice exposed to 4°C than those at room temperature (RT) (Figure 1C,D), consistent with elevated mitochondrial metabolism upon cold stress 29,30 . In addition, levels of Aco2 mRNA and activity were also detected in 3T3‐L1 cells during differentiation, showing stable expressions in the early differentiation period from day 0 to day 4, with increased levels in the late differentiation phase from day 4 to day 8 (Figure 1E,F), consistent with expression of mitochondrial proteins increased along with 3T3‐L1 cell differentiation 31 .…”

Charge-Dependent Strategy Enables a Single Fluorescent Probe to Study the Interaction Relationship between Mitochondria and Lipid Droplets

“…9−13 For instance, the mitochondria and LDs of the mice liver could work together to maintain the body temperature. 9 Meanwhile, the coat proteins of LDs, PLIN5, which are involved in lipolysis, are also present in mitochondria. 10 In addition, the mitochondrial outer membrane protein MIGA2 can link mitochondria to LDs in adipocytes.…”

“…Both mitochondria and lipid droplets (LDs) are important organelles in cells, each of which has its specific function. As an energy factory inside the cell, the mitochondria provide major energy for a variety of physiological activities within the cell. − On the other hand, LDs are the main storage site for neutral lipids in cells that play an important role in lipid metabolism and storage membrane transporter degradation. − Meanwhile, mitochondria and LDs also interact with one another in certain biological processes. − For instance, the mitochondria and LDs of the mice liver could work together to maintain the body temperature . Meanwhile, the coat proteins of LDs, PLIN5, which are involved in lipolysis, are also present in mitochondria .…”

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

“…A study of LDs and mitochondria isolated from the liver of mice housed at chronic cold stress determined that the mitochondrial TCA cycle and retinol metabolism were enhanced, while oxidative phosphorylation was not affected. Liver adaptation to cold stress conditions involved increased expression of Plin5 and MUPs (major urinary proteins), whereas expression of MPC was dramatically decreased [106]. Previously, the role of thermogenesis in the development of metabolic diseases was associated mostly with adipose tissues (interplay and transition between both white and brown) [107,108].…”

“…Previously, the role of thermogenesis in the development of metabolic diseases was associated mostly with adipose tissues (interplay and transition between both white and brown) [107,108]. However, the described cold-adaptation-related role of Plin5 also implies a role of the homeostasis and thermogenesis of liver lipids in NAFLD development [106].…”