Cold affects lipid metabolism and atherosclerosis through the mTORC1-SREBP2-PCSK9 pathway in brown adipose tissue

It's an intriguing subject why the risk of CVD increases in the winter. Lipids profile and plaque instability were measured, exhibiting that cold stimulation exacerbates high cholesterol state and accelerates the progression of AS. Metabolic parameters showed that high cholesterol impaired metabolism and reduces the resistance to cold. Cold stimulation activated BAT and converted WAT into Brite were testified by respiratory metabolism test and histopathological examination. Western blot, qRT-PCR and ELISA indicated that cold inhibited lipid clearance in the high cholesterol state and promotes SREBP2 and PCSK9 expression via mTORC1, while cold stimulation and high lipid synergistically promote the expression of PCSK9. Clinical data showed that coronary artery lesions and season elevated human plasma level of PCSK9.