# Metabolic effects of trehalose in mice of the C57BL/6 strain with obesity induced by a high carbohydrate-fat diet

## TL;DR

Trehalose had minimal effects on metabolic parameters in obese C57BL/6 mice fed a high carbohydrate-fat diet, suggesting limited utility for treating diet-induced obesity in humans.

## Contribution

The study evaluates trehalose's efficacy in a cafeteria diet-induced obesity model, relevant to human dietary obesity.

## Key findings

- Trehalose increased caloric intake in obese mice but did not reduce body weight or improve metabolic parameters.
- No significant changes in liver gene expression related to glucose transport, insulin sensitivity, or autophagy were observed.
- The cafeteria diet model showed signs of metabolic syndrome, but trehalose failed to counteract these effects.

## Abstract

The ability of trehalose to improve metabolic parameters in mice with experimental obesity has been shown to depend on the type of obesity model. In db/db mice, it reduced body weight, insulin, blood glucose, and cholesterol levels. In mice with obesity induced by high-fat dietary intake, it had no effect on body weight but reduced blood insulin levels with compensatory upregulation of insulin signaling gene expression. We studied the effect of trehalose on overweight and metabolic parameters in C57BL/6 inbred mice with obesity induced by a high carbohydrate-fat diet, the “cafeteria diet”. The cafeteria diet consisted of free access to water, standard chow, fatty foods (lard), and carbohydrates (biscuits) for 18 weeks. All mice were then randomly divided into four groups for four weeks of treatment: (1) water drinking, (2) drinking 3 % trehalose, (3) cafeteria diet and drinking water, (4) cafeteria diet and drinking 3 % trehalose. Alterations in body mass, food intake, fluid intake, dietary calories, blood biochemical parameters (glucose, triglyceride, cholesterol, HDL, ALT, creatinine levels), expression of carbohydrate metabolism (Slc2a2, Insr) and autophagy (Atg8, Becn1, Park2) genes in the liver were studied. The cafeteria diet obesity model was accompanied by some signs of metabolic syndrome as it induced an increase in body weight (by 25 %), calorie intake (by 25 %), blood levels of glucose (by 35 %), cholesterol (by 66 %), and triglycerides (by 23 %) in mice. Trehalose had little effect on control mice, causing a decrease in standard food intake and an increase in dietary caloric intake by the number of calories from trehalose itself. In obese mice, trehalose increased total caloric intake and biscuit consumption but had no substantial effect on body weight gain, blood metabolic parameters, or expression of liver genes regulating glucose transport (Slc2a2), insulin sensitivity (Insr), and autophagy processes (Atg8, Becn1, Park2). Since the cafeteria diet is the most adequate model of alimentary obesity development in humans, our results question the use of trehalose to correct the dietary type of obesity in humans.