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Increased Infiltration of Macrophages in Omental Adipose Tissue Is Associated With Marked Hepatic Lesions in Morbid Human Obesity

¹ Institut National de la Santé et de la Recherche Médicale (INSERM), U755 Nutriomique, Paris, France
² Pierre and Marie Curie-Paris 6 University, Faculty of Medicine, Les Cordeliers, IFR58, Paris, France
³ Nutrition Department, AP-HP, Hôtel-Dieu Hospital, Paris, France
⁴ Surgery Department, AP-HP, Hôtel Dieu Hospital, Paris, France
⁵ Anatomo-Pathology Department, AP-HP, Hôtel Dieu Hospital, Paris, France
⁶ Biochemistry Department, AP-HP, Hôtel Dieu Hospital, Paris, France
⁷ LIM and BIO, Paris 13 University, Bobigny, France
⁸ Pathology Department, AP-HP Beaujon Hospital, Clichy France
⁹ National Center for Scientific Research, Unité Mixte de Recherche 149, Paris, France

Address correspondence and reprint requests to Prof. Karine Clément, INSERM, U755 Nutriomique, Service de Nutrition, Hôtel-Dieu, 1 Place du Parvis Notre-Dame, 75004 Paris, France. E-mail: karine.clement{at}htd.ap-hop-paris.fr

Abbreviations: AST, aspartate aminotransferase; GT, -glutamyltranspeptidase; NAFLD, nonalcoholic fatty liver disease; QUICKI, quantitative insulin sensitivity check index; TBS-TC, Tris-buffered saline/Tween 20/casein 0.02 mol/l solution; TNF, tumor necrosis factor; WAT, white adipose tissue

In human obesity, white adipose tissue (WAT) is enriched in macrophages. How macrophage infiltration in WAT contributes to the complications of obesity is unknown. This study tested the hypothesis that recruitment of macrophages in omental WAT is associated with hepatic damage in obese patients. Paired biopsies of subcutaneous and omental WAT and a liver biopsy were collected during gastric surgery in 46 obese women and 9 obese men (BMI 47.9 ± 0.93 kg/m²). The number of HAM56+ macrophages in WAT was quantified microscopically, and correlations with clinical and biological parameters and histological liver pathology were investigated. There were twice as many macrophages in omental as in subcutaneous WAT (P < 0.0001). After adjustment for age, omental WAT macrophage infiltration was correlated to fasting glucose and insulin, quantitative insulin sensitivity check index, triglycerides, aspartate aminotransferase (AST), and -glutamyltranspeptidase. We propose an easy equation to estimate the amount of macrophages in omental WAT. Increased macrophage accumulation specifically in omental WAT was associated with hepatic fibroinflammatory lesions (P = 0.01). The best predictive model for the severity of hepatic damage includes adiponectinemia, AST, and omental WAT macrophages. These data suggest that the presence of macrophages in omental WAT participates in the cellular mechanisms favoring hepatic fibroinflammatory lesions in obese patients.

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