The transcription factor BLIMP1 promotes obesity and atherosclerosis by regulating macrophage adaptation to nutritional challenges

Here, we uncover a critical role for the transcription factor BLIMP in promoting ATM remodeling and function that impacts systemic lipid handling and obesity associated impairment of glycemic responses. BLIMP1 expression in humans and murine ATM is upregulated during obesity, and genetic ablation of BLIMP1 in murine macrophages led to increased energy expenditure and sex-independent resistance to fat mass accumulation.

BLIMP1 orchestrates ATM adaptation to nutritional input by promoting the differentiation of monocytes into maladapted macrophages with poor lipid handling capabilities and inflammatory potential, indirectly supporting obesity-associated adipocyte dysfunction and compromising systemic lipid homeostasis. BLIMP1 deficiency in monocytes and macrophages rescued glycemic responses in hyperphagic obese mice and lowered systemic cholesterol levels, mitigating the development of atherosclerosis in mice prone to hypercholesterolemia.