Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis

Abstract

Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride-derived fatty acids, generated by lipoprotein lipasemediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoElow-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. (Circ Res. 2016;118:173-182.

Diabetes incidence and glucose intolerance prevalence increase with higher outdoor temperature

“…8 Physiologically, BAT is activated by cold exposure. 9 10 Indeed, prolonged cold acclimatization recruits BAT activity 10 and is able to induce modest weight loss.…”

Brown Adipose Tissue: an Update on Recent Findings

“…Findings from mouse models demonstrate that cold-activated BAT can effectively clear plasma triglycerides [48–50] and may even mitigate hypercholesterinemia and suppress the formation of atherosclerotic plaque [51, 52, 49]. One study demonstrated a retardation of atherosclerotic plaque growth with only 8 weeks of cold exposure [53]; however, this may have been the result of rapid exposure instead of gradual acclimation.…”

The color of fat and its central role in the development and progression of metabolic diseases

“…In response to cold, norepinephrine is released from the sympathetic nervous system and binds to β adrenergic receptors on brown and beige adipocytes; this leads to the activation of the adenylyl cyclase/cAMP/protein kinase A (PKA) signaling cascade required for the hydrolysis of intracellular TG. PKA phosphorylates and activates cAMP response element-binding protein (CREB) resulting in enhanced transcription of UCP1 and peroxisome proliferator-activated receptor-γ [93]. Kuji et al [94] observed that patients with high plasma catecholamines, due to pheochromocytoma, during PET/CT exams have increased FDG uptake in the cervical, paravertebral, mediastinal, and perirenal regions, suggesting activation of BAT.…”