Phenotypic Switch of Adipose Tissue Macrophages as a Target to Reduce Obesity-Associated Metabolic Risk

KATHLEEN F. HINOJOSA VERA ; CHANDRU HEMAKUMAR; RAVINDRANATH S. BILACH; DARIO C. RAMIREZ; SANDRA E. GOMEZ MEJIBA

Preprints.org

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Lugar: BASEL; Año: 2025

2310-287X

Abstract: Obesity, a chronic inflammatory disease, is caused by a positive balance between energyintake and energy expenditure. Adipose tissue (AT) inflammation is the main cause of local andsystemic inflammation and oxidative stress and is the link between systemic inflammation andobesity-associated metabolic abnormalities, such as dyslipidemia, hypertension, insulin resistance(IR), fatty liver disease, and dysfunction of pancreatic β-cells. AT macrophages are derived from bonemarrow and blood monocytes that, upon arrival and under the pressure of the AT microenvironment,are differentiated into AT-associated macrophages (ATMs). The AT microenvironment in obesitycauses the activation of transcription factors that control the expression of a number of inflammatorygenes, leading to an ATM M1 phenotype or classically activated ATM. These M1 macrophagesexpress a number of proinflammatory genes and are the main cause of AT inflammation. Herein, wereviewed recently published information on the molecular mechanisms leading to the phenotypicswitch of macrophages under the pressure of obese AT. This information is needed to develop novelmechanism-based therapeutics to reduce AT inflammation and thus the metabolic risk associatedwith obesity.Keywords: obesity; adipose tissue; metaflammation; microenvironment; metabolic risk; macrophagephenotype; polarization