Carbohydrates to Prevent and Treat Obesity in a Murine Model of Diet-Induced Obesity

Abstract

<b><i>Introduction:</i></b> The biggest risk factor for obesity and its associated comorbidities is a Western diet. This Western diet induces adipose tissue (AT) inflammation, which causes an AT dysfunction. Since AT is a vital endocrine organ, its dysfunction damages other organs, thus inducing a state of chronic inflammation and causing various comorbidities. Even though it is evident a Western diet, high in fat and carbohydrates, induces obesity and its complications, it is not known yet which macronutrient plays the most important role. Therefore, the aim of this study was to investigate the effect of macronutrient composition on obesity and to reverse the Western diet-induced metabolic risk via caloric restriction (CR) or a change of diet composition. <b><i>Materials and Methods:</i></b> Male, C57BL/6JRj mice were fed with a diet high in fat, sucrose, fructose, sucrose and fructose, starch, a Western diet, or a control diet for 15 weeks. To assess reversibility of the metabolic risk, mice were first made obese via 15 weeks of WD and then put on either a CR or switched to a sucrose-rich diet. <b><i>Results:</i></b> A sucrose-rich and high-starch diet induced less obesity and a better metabolic profile than a Western diet, evidenced by less hepatic steatosis, lower plasma cholesterol, and less insulin resistance. Furthermore, these diets induced less intra-abdominal AT inflammation than a Western diet, since mRNA levels of pro-inflammatory markers were lower and there was less macrophage infiltration. Expression of tight junction markers in colon tissue was higher in the sucrose-rich and high-starch group than the Western group, indicating a better intestinal integrity upon sucrose-rich and high-starch feeding. Additionally, CR induced weight loss and decreased both metabolic abnormalities and AT inflammation, regardless of macronutrient composition. However, effects were more pronounced upon CR with sucrose-rich or high-starch diet. Even without CR, switching obese mice to a sucrose-rich diet induced weight loss and decreased AT inflammation and metabolic aberrations. <b><i>Discussion:</i></b> A diet high in sucrose or starch induces less obesity and obesity-associated complications. Moreover, switching obese mice to a sucrose-rich diet elicits weight loss and decreases obesity-induced metabolic complications, highlighting the potential of carbohydrates to treat obesity.

Diets Enriched in Sugar, Refined, or Whole Grain Differentially Influence Plasma Cholesterol Concentrations and Cholesterol Metabolism Pathways with Concurrent Changes in Bile Acid Profile and Gut Microbiota Composition in ApoE-/- Mice

“…These findings suggested that sugar-enriched diet may have an inhibitory effect on hepatic primary bile acid synthesis in comparison to RG-enriched diet. However, the circulating cholesterol concentrations were not significantly different between these two diets, which have been consistent with some ,, but not all studies, , utilizing the isocaloric substitution model between sucrose and starch. The reason for the discordant results between ours and previous studies may be attributed, in part, to the different sugar compositions.…”

Short‐term dietary intervention improves endothelial dysfunction induced by high‐fat feeding in mice through upregulation of the AMPK‐CREB signaling pathway

“…Herein, we demonstrate that the administration of a standard chow diet ad libitum for only 2 weeks after 6 weeks of HF diet exposure normalizes BW, adiposity, glucose and cholesterol levels, and glucose tolerance. Intriguingly, a recent study performed in a murine model of diet‐induced obesity supports that switching to a sucrose‐rich diet after western diet intake elicits weight loss and decreases obesity‐induced metabolic complications and points out the potential of carbohydrates to treat obesity 29 . However, we have recently evidenced that the nature of the carbohydrates and lipids included in the diet, and not only the amount of these macronutrients, is crucial to maintain cardiometabolic health 4 .…”

“…Intriguingly, a recent study performed in a murine model of diet-induced obesity supports that switching to a sucrose-rich diet after western diet intake elicits weight loss and decreases obesity-induced metabolic complications and points out the potential of carbohydrates to treat obesity. 29 However, we have recently evidenced that the nature of the carbohydrates and lipids included in the diet, and not only the amount of these macronutrients, is crucial to maintain cardiometabolic health. 4 These results are aligned with the 2019 Position Statement from the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) supporting healthy dietary patterns and includes the following recommendations: increased consumption of fiber-rich complex carbohydrates but limited intake of less healthy carbohydrate-rich foods, such as refined starches or sugars, a reduced consumption of saturated fat and a moderate intake of MUFA and PUFA, together with lowsalt and moderate alcohol consumption, and the promotion of physical exercise.…”