New Insights into How Adipocytes Sense their Triglyceride Stores. Is Cholesterol a Signal?

Abstract

In recent years, our view of adipose tissue has evolved from a passive sink for energy storage to an active tissue producing multiple molecules acting on various tissues in different aspects of energy homeostasis. The production of adipose-derived secretory products is tightly regulated as a function of adipocyte lipid accumulation, but the mechanisms by which fat cells are able to sense the levels of their triglyceride stores still remains largely unknown. This paper reviews new insights into this question taking cholesterol as a potential intracellular signaling molecule.

Disruption of Lipid Raft Function Increases Expression and Secretion of Monocyte Chemoattractant Protein-1 in 3T3-L1 Adipocytes

“…It has been reported that de novo cholesterol synthesis is limited in adipocytes [3]. Consistently, treatment with inhibitors that suppress cholesterol synthesis (mevastatin or U18666A) [7, 23] did not alter cholesterol levels in differentiated 3T3-L1 adipocytes even up to 24 h incubation (S1 Fig).…”

“…Additionally, we confirmed that MβCD and filipin treatment disturbed the integrity of lipid rafts in adipocytes (Fig 6C). Because cholesterol redistribution was observed in hypertrophied adipocytes [1–3, 5–7], the depletion of membrane cholesterol in obese adipocytes may result in a disturbance of the lipid raft function, leading to elevated MCP-1 expression and secretion and activation of proinflammatory signaling pathways such as ERK and NF-κB.…”

“…In fact, the adipose tissue is the largest pool of cholesterol in the human body [1, 2]. Moreover, the cholesterol found in the adipocytes is mostly in its free form, which distinguishes it from the cholesterol esters stored in the steroid hormone-producing adrenal cortical cells or cholesterol-laden foam cells [3]. Thus, the unique form and significant amount of cholesterol in adipocytes suggest a possible role for cholesterol in regulating adipocyte function.…”

“…Indeed, both cholesterol and triglycerides are elevated and accumulated in hypertrophied adipocytes [2, 4]. However, cholesterol is redistributed in these obese adipocytes, resulting in the depletion of cholesterol in the plasma membrane of hypertrophied adipocytes [1–3, 5–7]. Therefore, cholesterol imbalance may have an impact on adipocyte function during obesity or other disease conditions.…”

Differentially Expressed Genes Analysis of Brown Adipose Tissue During Cold Acclimation in Male Tree Shrews (Tupaia belangeri) based on RNA-Seq

“…Steroids were mainly composed of cholesterol. Studies have shown that insufficient cholesterol content could cause more free fatty acid (FFA) to remain in the circulatory system of mice to provide energy sources for other tissues and organs of the animal body (Dugail et al, 2003). In our study, compared with the control group, the squalene epoxidase (SQLE), lanosterol synthase (LSS), 24-dehydrocholesterol reductase (DHCR24), 7-dehydrocholesterol reductase (DHCR7), and lanosterol synthase (LSS) genes encoding proteins related to cholesterol synthesis were significantly down-regulated in the cold acclimation group.…”