Abstract

Introduction: Body mass index (BMI) and visceral adiposity cannot fully discriminate individuals at risk of presenting non-alcoholic fatty liver. Discordant visceral adiposity/liver fat phenotypes highlight the need for a better understanding of mechanisms involved in liver fat (LF) accumulation independent of BMI and visceral adipose tissue (VAT) quantity. Hypothesis: As VAT attenuation is a marker of VAT quality, we hypothesized that this marker would be an important determinant of LF accumulation and that a lower VAT attenuation would be associated with an increased LF accumulation irrespective of BMI and VAT area. Methods: Analyses included 3002 participants (51% men) aged 40 to 70 years with BMI values between 18.5 and 40.0 kg/m 2 of INSPIRE ME-IAA, a prospective observational study conducted in 29 countries in America, Asia, and Europe. Computed tomography was used to measure subcutaneous adipose tissue (SAT) and VAT area and attenuation (a marker of adipocyte size) and liver attenuation (a marker of LF content). Participants’ cardiometabolic health profile was assessed in the fasting state. Partial Pearson correlation coefficients were computed to document the associations between VAT area and attenuation and liver attenuation. Multivariable regression analyses were performed to quantify the contribution of SAT and VAT area and attenuation to LF attenuation. A mixed-model ANOVA was used to compare liver attenuation according to VAT area and attenuation, and to compare VAT attenuation according to LF level and VAT area. A generalized linear mixed model was used to compare the prevalence of type 2 diabetes according to LF content and VAT area. Results: VAT attenuation was associated with liver attenuation in women (r=0.34, p<0.0001; r=0.38, p<0.0001; r=0.36, p<0.0001) and men (r=0.42, p<0.0001; r=0.30, p<0.0001; r=0.24, p<0.0001) within each BMI category (normal weight, overweight, obesity), respectively. VAT attenuation better explained LF attenuation than SAT and VAT area. A low VAT attenuation was associated with a lower liver attenuation within each VAT area tertile in all BMI categories (p<0.05). Furthermore, an increased LF content was associated with a lower VAT attenuation (p<0.05) independent of SAT and VAT area in both sexes in all BMI categories. An increased LF content was also associated with a higher prevalence of type 2 diabetes (p<0.05) in individuals with normal weight and overweight beyond VAT area. Conclusion: A low VAT attenuation reflecting larger adipocytes is associated with an increased LF content and risk of type 2 diabetes independent of BMI and VAT area. These results suggest that VAT attenuation as a marker of adipose tissue quality might be involved in the development of non-alcoholic fatty liver disease.

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