Impact of dietary sucrose on adiposity and glucose homeostasis in C57BL/6J mice depends on mode of ingestion: liquid or solid

Abstract

Objective Although it is widely accepted that obesity results from an imbalance of energy intake and expenditure, the mechanisms underlying this process and effective strategies for prevention and treatment are unclear. Growing evidence suggests excess consumption of sugar may play an important role, yet we showed previously in mice that consuming up to 30% of calories as sucrose in the diet had no impact on weight regulation. Since in humans consumption of sugar-sweetened beverages has been widely implicated, we investigated whether the mode of ingestion (solid or liquid) had different impacts on body weight regulation and glucose homeostasis. Methods Dietary sucrose was delivered in solid (as part of a standard pelleted rodent chow) and liquid (in drinking water) to C57BL/6 mice for 8 weeks. Body weight, body composition, energy intake and expenditure were monitored, as well as glucose and insulin tolerance tests. Expression of sweet taste receptors on the tongue, and glycogen and fat contents of the liver were also measured. Results Consumption of sucrose-sweetened water, but not equivalent levels of solid sucrose, led to body fat gain in C57BL/6 mice. Glucose intolerance was positively correlated to body fatness, rather than sucrose intake. Conclusions Our data support the suggestion that consumption of liquid sucrose may be an important contributor to dysregulation of body weight and related metabolic syndromes.

Chronic high dietary sucrose induces sexually dimorphic metabolic adaptations in liver and adipose tissue

“…In addition to the effects we observed on lipid metabolism, we ( Figure 1D and Supplementary Figure 1) and others (Burke et al, 2018;Maekawa et al, 2017;Togo et al, 2019) have shown that energy expenditure increases in response to liquid sucrose intake. Given our observation of a disconnect between energy intake, energy expenditure and adiposity in the absence of any impairments to systemic insulin sensitivity following chronic liquid sucrose intake, we sought to determine if microbial metabolism might explain some of these metabolic adaptations.…”

“…Although dietary sugars have been used extensively to induce cardiometabolic abnormalities in animal models (Bacon et al, 1984;Bukowiecki et al, 1983;Burke et al, 2018;Chen et al, 2019;Kawasaki et al, 2009;Oliveira et al, 2014;Ritze et al, 2014;Softic et al, 2019;Togo et al, 2019), the molecular mechanisms underlying sugar-induced hepatic lipid accumulation remain poorly understood in a context that is translational to human dietary practices (Choo and Sievenpiper, 2015). Most preclinical studies rely upon use of supraphysiologic concentrations of sucrose, glucose or fructose to induce steatosis and other metabolic comorbidities (Chen et al, 2011;Choo and Sievenpiper, 2015;Softic et al, 2019;Soria et al, 2001), often with the confounding addition of excess dietary lipid (Chen et al, 2011;Oliveira et al, 2014;Softic et al, 2019).…”

“…Most preclinical studies rely upon use of supraphysiologic concentrations of sucrose, glucose or fructose to induce steatosis and other metabolic comorbidities (Chen et al, 2011;Choo and Sievenpiper, 2015;Softic et al, 2019;Soria et al, 2001), often with the confounding addition of excess dietary lipid (Chen et al, 2011;Oliveira et al, 2014;Softic et al, 2019). This lack of translatability, in combination with reports that the effects of dietary sugars are dependent on physical form (i.e., liquid versus solid) (Ritze et al, 2014;Togo et al, 2019), make it difficult to draw mechanistic conclusions applicable to how sugar intake leads to NAFLD in humans.…”

“…Most circulating non-esterified fatty acids (NEFA) are derived from adipose tissue lipolysis (van Hall et al, 2002). Adipose tissue mass increases rapidly in response to sucrose intake (Bukowiecki et al, 1983;Chen et al, 2011;Oliveira et al, 2014), whereas increased adiposity following sucrose feeding in humans (Smith et al, 1973) and rats (Soria et al, 2001) leads to an increase in the rate of adipose tissue lipolysis ex vivo.…”

Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective

“…75 84 Furthermore, a study using male C57BL/6J mice (8 weeks old) suggested that distinct modes of sucrose delivery differentially affected body regulation and glucose homeostasis. 134 The authors showed that mice exposed to a liquid sucrose solution (50% sucrose in the water plus 30% calories from sucrose in solid food)…”