The “metabolically healthy obese” and “metabolically-unhealthy normal-weight” phenotypes: opposite sides of the same coin?

Faidon Magkos is Associate Professor at the Department of Nutrition, Exercise and Sports at the University of Copenhagen.

It has become apparent in recent years that excess total body weight and fat do not necessarily impair metabolic function and increase risk for cardiometabolic disease; and vice versa, absence of excess weight and fat do not necessarily entail low risk. A subset (~30%) of people with obesity do not present with metabolic abnormalities such as hyperglycemia, hyperinsulinemia, and dyslipidemia, or hypertension (“metabolically healthy obese”); whereas a subset (~20%) of people with normal body weight do present with these metabolic abnormalities (“metabolically-unhealthy normal-weight”). Compared with BMI-matched control groups, metabolically healthy obese subjects have lower accumulation of fat in the liver, better physical fitness, and a tight coordination between the pancreas (insulin secretion) and skeletal muscle (insulin sensitivity) to maintain glucose homeostasis; whereas conversely, metabolically-unhealthy normal-weight subjects have more liver fat, inferior fitness, and dysregulated glucose homeostasis.  

Of interest, there is also evidence suggesting that the ability to store excess calories in lower body adipose tissue is increased in metabolically healthy obese subjects and decreased in metabolically-unhealthy normal-weight subjects. This implicates local adipose tissue fatty acid uptake and release as a key determinant not only of body fat distribution, but also metabolic function.  

Understanding the traits of these phenotypes will have important implications for research but also clinical practice, as it will identify possible targets for pharmacological intervention that can help minimize the burden of metabolic disease in people with and without obesity. 

Moderator: Simon Dankel

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