Abstract
Obesity may not be consistently associated with metabolic disorders and mortality later in life, prompting exploration of the challenging concept of healthy obesity. Here, the consumption of a high-fat/high-sucrose (HF/HS) diet produces hyperglycaemia and hypercholesterolaemia, increases oxidative stress, increases endotoxaemia, expands adipose tissue (with enlarged adipocytes, enhanced macrophage infiltration and the accumulation of cholesterol and oxysterols), and reduces the median lifespan of obese mice. Despite the persistence of obesity, supplementation with a polyphenol-rich plant extract (PRPE) improves plasma lipid levels and endotoxaemia, prevents macrophage recruitment to adipose tissues, reduces adipose accumulation of cholesterol and cholesterol oxides, and extends the median lifespan. PRPE drives the normalization of the HF/HS-mediated functional enrichment of genes associated with immunity and inflammation (in particular the response to lipopolysaccharides). The long-term limitation of immune cell infiltration in adipose tissue by PRPE increases the lifespan through a mechanism independent of body weight and fat storage and constitutes the hallmark of a healthy adiposity trait.
Highlights
Obesity is characterized by the accumulation of adipose tissue and has long been associated with a significantly higher all-cause mortality rate, mostly due to metabolic diseases and cardiovascular complications[1]
The healthy obesity concept remains an open question in light of (1) the harmful consequences of adipose tissue hypertrophy that may vary between individuals, (2) increased numbers of metabolic abnormalities that still occur in some lean individuals, (3) the lack of typical metabolic obesity-associated complications in some overweight subjects, and (4) the identification of tissue-specific gene co-expression networks that allow researchers to distinguish between healthy and unhealthy obese individuals[5,6,7]
A primary goal of the present study was to assess the impact of obesity induced by the consumption of an experimental diet on the adipose tissue composition and longevity in mice fed a high-fat/high-sucrose (HF/HS) diet compared to healthy, control mice fed standard show (Std)
Summary
Obesity is characterized by the accumulation of adipose tissue and has long been associated with a significantly higher all-cause mortality rate, mostly due to metabolic diseases and cardiovascular complications[1]. Researchers have not established whether healthy obesity exists and translates into fewer metabolic abnormalities, better health and increased lifespan independent of adiposity compared to unhealthy obesity, and the cellular and molecular mechanisms must be deciphered These questions require designed experimental models in which the adipose tissue accumulation and composition are controlled and monitored. Because even a minimal weight loss was previously shown to be sufficient to reduce obesity-related disorders, a major requirement here was to maintain identical elevated weights in control and treated obese groups throughout the study to explore adipose tissue function (with a specific emphasis on immune cell infiltration and lipid metabolism) in the absence of confounding factors. This strategy allowed us to revisit the myth of innocent obesity[16] in a well-controlled model of diet-induced obesity
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