Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models

Hematopoietic ABCA1 deletion promotes monocytosis and worsens diet-induced insulin resistance in mice

“…Our BM transplantation studies involve the depletion of ABCA1 in all hematopoietic cells. In contrast, the myeloid-specifi c M lysozyme promoter used to drive Cre expression is restricted to macrophages and neutrophils ( 33 ). This suggests that the increased infl ammation and decreased insulin sensitivity observed in mice receiving ABCA1-null BM is attributable to loss of ABCA1 in other cell types or to loss of ABCA1 in cells in addition to macrophages.…”

Rewiring of Lipid Metabolism in Adipose Tissue Macrophages in Obesity: Impact on Insulin Resistance and Type 2 Diabetes

“…While seemingly logic, these results have been contested by experiments conducted in myeloid Abca1 KO and Wt mice who developed similar IR, hypercholesterolemia and hepatic steatosis. Although ATM in the SVF from myeloid Abca1 -/mice did accumulate more Chol than their Wt counterparts, neither macrophage infiltration nor inflammatory Tnfα, Mcp-1 and Il-1β cytokine expression was different [64]. These differences could be attributed to a number of factors (i.e., hematopoietic vs. myeloid targeting, content and length of the diet, Abca1/g1 levels in AT only vs. in ATM).…”

Adipose Modulation of ABCG1 Uncovers an Intimate Link Between Sphingomyelin and Triglyceride Storage

“…This contrasted with the adipose cholesterol accumulation observed in adipose ABCA1 deficiency driving an upregulation of LXR target genes such as ABCG1 (21). So, this raises the question: Where did the cholesterol go in ABCG1-deficient adipocytes?…”

“…Altogether these studies point to an overall consensus in which a defective cholesterol efflux pathway is associated with reduced fat storage, an effect that could be attributed to adipose cachexia (20). However, recent studies suggest that myeloid-specific ABCA1 deletion does not alter diet-induced obesity (21), and paradoxically, specific adipocyte ABCA1 deficiency leads to increased body weight gain and fat storage in response to diet-induced obesity due to adipose cholesterol accumulation altering lipolysis (22) (Fig. 1).…”