Metabolic phenotyping in people living with obesity: Implications for dietary prevention

Abstract

Given the increasing number of people living with obesity and related chronic metabolic disease, precision nutrition approaches are required to increase the effectiveness of prevention strategies. This review addresses these approaches in different metabolic phenotypes (metabotypes) in obesity. Although obesity is typically associated with an increased cardiometabolic disease risk, some people with obesity are relatively protected against the detrimental effects of excess adiposity on cardiometabolic health, also referred to as 'metabolically healthy obesity' (MHO). Underlying mechanisms, the extent to which MHO is a transient state as well as lifestyle strategies to counteract the transition from MHO to metabolically unhealthy obesity (MUO) are discussed. Based on the limited resources that are available for dietary lifestyle interventions, it may be reasonable to prioritize interventions for people with MUO, since targeting high-risk patients for specific nutritional, lifestyle or weight-loss strategies may enhance the cost-effectiveness of these interventions. Additionally, the concept of tissue insulin resistant (IR) metabotypes is discussed, representing distinct etiologies towards type 2 diabetes (T2D) as well as cardiovascular disease (CVD). Recent evidence indicates that these tissue IR metabotypes, already present in individuals with obesity with a normal glucose homeostasis, respond differentially to diet. Modulation of dietary macronutrient composition according to these metabotypes may considerably improve cardiometabolic health benefits. Thus, nutritional or lifestyle intervention may improve cardiometabolic health, even with only minor or no weight loss, which stresses the importance of focusing on a healthy lifestyle and not on weight loss only. Targeting different metabotypes towards T2D and cardiometabolic diseases may lead to more effective lifestyle prevention and treatment strategies. Age and sex-related differences in tissue metabotypes and related microbial composition and functionality (fermentation), as important drivers and/or mediators of dietary intervention response, have to be taken into account. For the implementation of these approaches, more prospective trials are required to provide the knowledge base for precision nutrition in the prevention of chronic metabolic diseases.

Keywords: Cardiometabolic risk; Metabolically (un)healthy obesity; Metabotype; Precision nutrition; Tissue-specific insulin resistance.

Fig. 1

Body fat distribution is a key determinant of cardiometabolic disease risk. Subcutaneous adipose tissue buffers the daily influx of excess calories during a prolonged positive energy balance. Upper body fat storage in people with abdominal obesity (that is, predominant lipid storage in the abdominal region) is usually paralleled by more lipid spillover in the circulation, an increase in visceral adipose tissue and ectopic fat storage (that is, lipid accumulation in non-adipose such as skeletal muscle, liver, pancreas and heart), which instigates the development of insulin resistance and chronic cardiometabolic diseases such as type 2 diabetes and cardiovascular diseases. In contrast, predominant fat storage in the lower body as seen in people with lower body obesity limits lipid spillover in the circulation, since gluteo-femoral adipose tissue acts as a metabolic sink to buffer excess lipids. Consequently, less lipids will accumulate in visceral adipose tissue and certain non-adipose tissues, thereby reducing cardiometabolic disease risk. Premenopausal women living with obesity seem to be characterized by more lipid accumulation in skeletal muscle (smaller lipid droplets consisting of less saturated fatty acids) and similar or less lipid storage in the liver, with less detrimental effects on tissue-specific insulin sensitivity compared to men with obesity. Created with BioRender.com

Fig. 2

The depicted precision nutrition concept is based on the definition of tissue metabotypes related to parameters of tissue-specific metabolism like MIR, LIR and adipose IR, tissue fat accumulation and microbial composition; this strategy will improve insulin sensitivity, blood glucose homeostasis and cardiometabolic risk compared to current, one-size-fits-all dietary guidelines in the population with overweight. Created with BioRender.com