The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function

Abstract

The current obesity epidemic poses a major public health issue since obesity predisposes towards several chronic diseases. BMI and total adiposity are positively correlated with cardiometabolic disease risk at the population level. However, body fat distribution and an impaired adipose tissue function, rather than total fat mass, better predict insulin resistance and related complications at the individual level. Adipose tissue dysfunction is determined by an impaired adipose tissue expandability, adipocyte hypertrophy, altered lipid metabolism, and local inflammation. Recent human studies suggest that adipose tissue oxygenation may be a key factor herein. A subgroup of obese individuals - the 'metabolically healthy obese' (MHO) - have a better adipose tissue function, less ectopic fat storage, and are more insulin sensitive than obese metabolically unhealthy persons, emphasizing the central role of adipose tissue function in metabolic health. However, controversy has surrounded the idea that metabolically healthy obesity may be considered really healthy since MHO individuals are at increased (cardio)metabolic disease risk and may have a lower quality of life than normal weight subjects due to other comorbidities. Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases.

Keywords: Adipose tissue function; Body fat; Metabolic health; Obesity; Oxygen.

Fig. 1

Differences in adipose tissue function and body fat distribution between MHO and metabolically unhealthy obese individuals. Expansion of adipose tissue does not necessarily translate into metabolic abnormalities. A subgroup of individuals with obesity, referred to as MHO individuals, is relatively protected against the development of cardiometabolic diseases as compared to metabolically unhealthy obese subjects. Emerging evidence suggests that alterations in adipose tissue function and body fat distribution are key factors underlying the metabolically unhealthy obese phenotype. Metabolically unhealthy obese individuals are characterized by lower subcutaneous fat mass, adipocyte hypertrophy, a pro-inflammatory adipose tissue phenotype and an impaired fat storage capacity of adipose tissue, which may result in ectopic fat deposition (i.e., more visceral fat, lipid accumulation in the liver and skeletal muscle) and inflammation in visceral adipose tissue, thereby contributing to the development of insulin resistance and chronic cardiometabolic diseases. ASAT = abdominal subcutaneous adipose tissue; FSAT = femoral subcutaneous adipose tissue; VAT = visceral adipose tissue.