Myeloid-specific CAMKK2 deficiency protects against diet-induced obesity and insulin resistance by rewiring metabolic gene expression and enhancing energy expenditure

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective Obesity is associated with chronic, low-grade inflammation in metabolic tissues such as liver, adipose tissue and skeletal muscle implicating insulin resistance and type 2 diabetes as inflammatory diseases. This inflammatory response involves the accumulation of pro-inflammatory macrophages in these metabolically relevant organs. The Ca 2+ -calmodulin-dependent protein kinase kinase-2 (CAMKK2) is a key regulator of cellular and systemic energy metabolism, and a coordinator of macrophage-mediated inflammatory responses. However, its role in obesity-associated metabolic dysfunction is not fully defined. The aim of this study was to determine the contribution of CAMKK2 to the regulation of inflammation and systemic metabolism during diet-induced obesity. Methods Mice with myeloid-specific deletion of Camkk2 were generated and challenged with a high-fat diet. Metabolic phenotyping, histological analyses, and transcriptomic profiling were used to assess whole-body metabolism, liver lipid accumulation, and gene expression in macrophages and adipose tissue. Results Myeloid-specific Camkk2 deficiency protected mice from high fat diet-induced obesity, insulin resistance and liver steatosis. These protective effects were associated with rewiring of metabolic and inflammatory gene expression in both macrophages and adipose tissue, along with enhanced whole-body energy expenditur

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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