Suppression of adipocyte ABHD6 favors anti-inflammatory and adipogenic programs to preserve adipose tissue fitness in obesity

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)

Some individuals exhibit metabolically healthy obesity, characterized by the expansion of white adipose tissue (WAT) without associated complications. The monoacylglycerol (MAG) hydrolase α/β-hydrolase domain-containing 6 (ABHD6) has been implicated in energy metabolism, with its global deletion conferring protection against obesity. However, the immunometabolic roles of adipocyte ABHD6 in WAT remodeling in response to nutri-stress and obesity are not known. Here, we demonstrate that in insulin resistant women, ABHD6 mRNA expression is elevated in visceral fat and positively correlates with obesity and metabolic dysregulation. ABHD6 expression is also elevated in the WATs of diet-induced obese and db/db mice. Although adipocyte-specific ABHD6 knockout (AA-KO) mice become obese under high-fat diet, they show higher plasma adiponectin, reduced circulating insulin and inflammatory markers, improved insulin sensitivity, and lower plasma and liver triglycerides. They also show enhanced insulin action in various tissues, but normal glucose tolerance. In addition, AA-KO mice display healthier and less inflamed expansion of visceral fat, with smaller adipocytes and higher stimulated lipolysis and fatty acid oxidation levels. Similar but less prominent phenotype was found in the subcutaneous and brown fat depots. Thus, adipocyte ABHD6 suppression prevents most of the metabolic and infla

Evidence level

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

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