Excess fructose intake‐induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals

Abstract

We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro-and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-c2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity.

Deleterious Metabolic Effects of High Fructose Intake: The Preventive Effect of Lactobacillus kefiri Administration

“…In fact, the use of probiotics as a preventive tool has been addressed mostly in high-fat diet models. FRD has been widely used to induce MS and obesity in animal models [7,8,11]. Our current results show that FRD intake for six weeks was effective in inducing an increase in body weight and EAT mass.…”

“…Modern diets are characterized by high carbohydrate intake, especially fructose-sweetened beverages, and have been associated with high prevalence of overweight and Metabolic Syndrome (MS) in humans [6]. High-fructose feeding has been widely used in animal models to induce obesity and MS phenotype [7,8,9,10]. In the present study, we used a fructose-rich diet intake (FRD, 20% w / v in drinking water), which is far from fructose intake by humans, to generate a mice model of obesity.…”

“…In the present study, we used a fructose-rich diet intake (FRD, 20% w / v in drinking water), which is far from fructose intake by humans, to generate a mice model of obesity. Previously, FRD has been related to the development of insulin resistance, dyslipidemias, increased abdominal AT mass, and changes in the pattern of AT adipokine secretion [7,8,11]. Partly, these metabolic disorders are a consequence of fructose-induced hepatic de novo lipogenesis, and the resulting increase in AT fatty acid uptake [12,13].…”

White Adipose Tissue and Circadian Rhythm Dysfunctions in Obesity: Pathogenesis and Available Therapies

“…the RPAT pad has 2 adipocyte populations: one similar to and another larger than the ones identified in the normal (control) group, thus suggesting that this AT pad mass expansion could result from a combination of newly generated adipocytes (adipogenesis) and hypertrophy of the existing ones [22, [31][32][33] .…”

Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway

“…Diabetes, dyslipidemia and obesity have been known as important factors for the atherosclerosis development [4]. High-fructose feeding is indicated to result in metabolic syndrome characterized by hyperleptinemia, hyperinsulinemia, and insulin resistance, contributing to the development of type 2 diabetes in animals [5,6]. However, up until now the specific molecular mechanism causing the disease of atherosclerosis is not fully understood.…”