mTORC1 restrains adipocyte lipolysis to prevent systemic hyperlipidemia

Area of Science:

• Cell Biology
• Metabolic Research
• Lipid Metabolism

Background:

• mTORC1 signaling plays a role in lipid metabolism, but its precise function in hyperlipidemia is unclear.
• mTORC1 inhibitors are used clinically but cause hyperlipidemia as a side effect.

Purpose of the Study:

• To investigate the role of adipocyte mTORC1 signaling in systemic lipid homeostasis.
• To elucidate the mechanisms by which mTORC1 influences lipid metabolism in vivo.

Main Methods:

• Generated mice with adipocyte-specific knockout of Raptor (mTORC1 subunit) or ATGL (lipolytic enzyme), or both.
• Characterized systemic lipid metabolism, including triglyceride and cholesterol levels, in these mouse models.

Main Results:

• Mice lacking adipocyte mTORC1 activity exhibited hypertriglyceridemia and hypercholesterolemia due to failed suppression of lipolysis.
• Inhibition of lipolysis in these mice normalized lipid levels and improved triglyceride clearance.

Conclusions:

• Unsuppressed adipose lipolysis in the fed state contributes to hyperlipidemia by impairing triglyceride clearance.
• Adipose tissue mTORC1 signaling is essential for suppressing lipolysis and maintaining systemic lipid homeostasis.