Abstract
Non-shivering thermogenesis is an energy demanding process that primarily occurs in brown and beige adipose tissue. Beyond regulating body temperature, these thermogenic adipocytes regulate systemic glucose and lipid homeostasis. Historically, research on thermogenic adipocytes has focused on glycolytic metabolism due to the discovery of active brown adipose tissue in adult humans through glucose uptake imaging. The importance of lipids in non-shivering thermogenesis has more recently been appreciated. Uptake of circulating lipids into thermogenic adipocytes is necessary for body temperature regulation and whole-body lipid homeostasis. A wide array of circulating lipids contribute to thermogenic potential including free fatty acids, triglycerides, and acylcarnitines. This review will summarize the mechanisms and regulation of lipid uptake into brown adipose tissue including protein-mediated uptake, lipoprotein lipase activity, endocytosis, vesicle packaging, and lipid chaperones. We will also address existing gaps in knowledge for cold induced lipid uptake into thermogenic adipose tissue.
Highlights
Endotherms maintain their body temperature by producing heat through both shivering and non-shivering thermogenesis
In hyperlipidemic mice modeled by KO of the extracellular lipolysis stimulator apolipoprotein AV (Apoa5), cold exposure led to reduced levels of TGs and cholesterol in the plasma accompanied by an influx into the brown adipose tissue (BAT) (Bartelt et al, 2011; Berbée et al, 2015)
This hypothesis is supported by demonstration of diffusion through fluorescent long chain fatty acids (LCFAs) uptake in lipid vesicles pretreated with inhibitors of fatty acids (FAs) transporters, two of which were direct competitive inhibitors for Cluster of Differentiation 36 (CD36) (Jay et al, 2020)
Summary
Non-shivering thermogenesis is an energy demanding process that primarily occurs in brown and beige adipose tissue. These thermogenic adipocytes regulate systemic glucose and lipid homeostasis. Research on thermogenic adipocytes has focused on glycolytic metabolism due to the discovery of active brown adipose tissue in adult humans through glucose uptake imaging. Uptake of circulating lipids into thermogenic adipocytes is necessary for body temperature regulation and whole-body lipid homeostasis. A wide array of circulating lipids contribute to thermogenic potential including free fatty acids, triglycerides, and acylcarnitines. This review will summarize the mechanisms and regulation of lipid uptake into brown adipose tissue including protein-mediated uptake, lipoprotein lipase activity, endocytosis, vesicle packaging, and lipid chaperones. We will address existing gaps in knowledge for cold induced lipid uptake into thermogenic adipose tissue
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