Obesity is an established a predisposing factor for chronic disease processes including metabolic syndrome, type 2 diabetes (T2D), cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). These sequelae of obesity results from the relationship between excess adiposity, underlying inflammation and insulin resistance at the population level. 
More recently, however, research indicates there is more to learn about obesity as a risk factor for these disease processes on the individual level, since the number of lean phenotypes suffering the same health conditions as obese phenotypes is on the rise. A 2016 study found that unhealthy (lean or obese) individuals, characterized by the presence of metabolic syndrome markers, had higher liver fat levels and more factors related to subclinical systolic and diastolic blood pressure dysfunction. The data from this publication may partly explain why some phenotypes, lean and obese, are more prone to CVD risk when associated with poor metabolic health, regardless of BMI or fat mass. 
It is becoming clear that when treating the individual, it is more important to focus on the distribution of body fat and the adipose tissue function, rather than BMI alone, as the former are better predictors of insulin resistance and downstream complications including NAFLD.
Adipose tissue dysfunction is related to local inflammation, altered lipid metabolism, adipocyte hypertrophy and impairment in adipose tissue expandability. In fact, levels of adipose tissue oxygenation may be a key factor to understanding this nuanced relationship. Those individuals who are obese, yet classified as healthy (metabolically healthy obese [MHO]), have been found to have better adipose tissue function, less ectopic fat storage and higher insulin sensitivity, thus reducing their risk of cardiometabolic characteristics and other related disease processes such as NAFLD.
A meta-analysis of 15 studies combined with data from a 2017 study, totaling over 23,800 patients, divided subject data into groups consisting of individuals with NAFLD (lean and obese) and compared them to control lean and obese subjects without NAFLD. When compared to lean non-NAFLD controls, lean NAFLD patients were older and exhibited the full spectrum of metabolic syndrome abnormalities, with higher:
- Plasma glucose levels
- HOMA-IR (surrogate measure of insulin resistance)
- Blood lipids
- Systolic and diastolic blood pressure
- Waist circumference
These metabolic alterations were significantly worse in obese patients vs. lean patients, independent of NAFLD.
This publication concluded that lean and obese patients with NAFLD share metabolic and cardiovascular aberrations, and that the lean NAFLD patient, although presenting with normal BMI, may carry excess abdominal adipose tissue and other metabolic syndrome features.
Why is this Clinically Relevant?
- Practitioners should screen all patients, lean and obese, for cardiometabolic risk factors
- Insulin resistance, fat mass deposition and adipocyte function may be more accurate predictors of NAFLD risk than BMI and total fat mass
- Unhealthy lean individuals may have similar underlying metabolic syndrome risk factors as unhealthy obese individuals for cardiometabolic disease states
Sookoian S, Pirola CJ. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther. 2017 Jul;46(2):85-95. doi: 10.1111/apt.14112. Epub 2017 May 2.
 Goossens GH. The Metabolic Phenotype in Obesity: Fat Mass, Body Fat Distribution, and Adipose Tissue Function. Obes Facts. 2017;10(3):207-215. doi: 10.1159/000471488. Epub 2017 Jun 1.
 Dobson R, et al. Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity. Int J Obes (Lond) 2016 Jan;40(1):153-61. doi: 10.1038/ijo.2015.151. Epub 2015 Aug 14.
 Sookoian S, Pirola CJ. Systematic review with meta-analysis: risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther. 2017 Jul;46(2):85-95. doi: 10.1111/apt.14112. Epub 2017 May 2.