Low-Fat, High-Carbohydrate Diets Reduce Body Weight and Sperm Count but Increase Sperm Motility in Mice.

BACKGROUND: Male reproduction is impacted by both over- and under-nutrition, demonstrated by animal studies using high-fat and low-protein dietary interventions. Little is known about the impacts of low-fat, high-carb diets and types of dietary carbohydrates on sperm traits. OBJECTIVES: Using a nutritional geometry approach, we investigated the effects of partially or completely substituting glucose for fructose in isocaloric diets containing either 10%, 20%, or 30% fat (by energy) on sperm traits in mice. METHODS: Male C57BL/6J mice were fed 1 of 15 experimental diets for 18 wk starting from 8 wk of age. Reproductive organs were then harvested, and sperm concentration, motility, and velocity were measured using Computer-Assisted Sperm Analysis. RESULTS: Increasing dietary fat from 10% to 30% while maintaining energy density at 14.3 kJ/g and protein content at 20% resulted in increased body weight and sperm production but reduced the percentage of motile sperm. Body weight and seminal vesicle weight were maximized on diets containing a 50:50 mix of fructose and glucose, but carbohydrate type had few significant impacts on epididymal sperm traits. CONCLUSIONS: The opposing impacts of dietary fat on mouse sperm quantity and quality observed suggest that male fertility may not be optimized by a single diet; rather, context-specific dietary guidelines targeted to specific concerns in semen quality may prove useful in treating male infertility.

Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice.

The metabolic effects of sugars and fat lie at the heart of the "carbohydrate vs fat" debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n = 245) are maintained on one of 18 isocaloric diets for 18-19 weeks and their metabolic status is assessed through in vivo procedures and by in vitro assays involving harvested tissue samples. We find that in the setting of low and medium dietary fat content, a 50:50 mixture of fructose and glucose (similar to high-fructose corn syrup) is more obesogenic and metabolically adverse than when either monosaccharide is consumed alone. With increasing dietary fat content, the effects of dietary sugar composition on metabolic status become less pronounced. Moreover, higher fat intake is more harmful for glucose tolerance and insulin sensitivity irrespective of the sugar mix consumed. The type of fat consumed (soy oil vs lard) does not modify these outcomes. Our work shows that both dietary fat and sugars can lead to adverse metabolic outcomes, depending on the dietary context. This study shows how the principles of the two seemingly conflicting models of obesity (the "energy balance model" and the "carbohydrate insulin model") can be valid, and it will help in progressing towards a unified model of obesity. The main limitations of this study include the use of male mice of a single strain, and not testing the metabolic effects of fructose intake via sugary drinks, which are strongly linked to human obesity.

Impact of dietary carbohydrate type and protein-carbohydrate interaction on metabolic health.

Reduced protein intake, through dilution with carbohydrate, extends lifespan and improves mid-life metabolic health in animal models. However, with transition to industrialised food systems, reduced dietary protein is associated with poor health outcomes in humans. Here we systematically interrogate the impact of carbohydrate quality in diets with varying carbohydrate and protein content. Studying 700 male mice on 33 isocaloric diets, we find that the type of carbohydrate and its digestibility profoundly shape the behavioural and physiological responses to protein dilution, modulate nutrient processing in the liver and alter the gut microbiota. Low (10%)-protein, high (70%)-carbohydrate diets promote the healthiest metabolic outcomes when carbohydrate comprises resistant starch (RS), yet the worst outcomes were with a 50:50 mixture of monosaccharides fructose and glucose. Our findings could explain the disparity between healthy, high-carbohydrate diets and the obesogenic impact of protein dilution by glucose-fructose mixtures associated with highly processed diets.

Ingestion of resistant starch by mice markedly increases microbiome-derived metabolites.

Recent research has shown significant health benefits deriving from high-dietary fiber or microbiome-accessible carbohydrate consumption. Compared with native starch (NS), dietary resistant starch (RS) is a high microbiome-accessible carbohydrate that significantly alters the gut microbiome. The aim of this study was to determine the systemic metabolic effects of high microbiome-accessible carbohydrate. Male C57BL/6 mice were divided into 2 groups and fed either NS or RS for 18 wk (n = 20/group). Metabolomic analyses revealed that plasma levels of numerous metabolites were significantly different between the RS-fed and NS-fed mice, many of which are microbiome-derived. Most strikingly, we observed a 22-fold increase in gut microbiome-derived tryptophan metabolite indole-3-propionate (IPA), which was positively correlated with several gut microbiota, including Allobaculum, Bifidobacterium, and Lachnospiraceae, with Allobaculum having the most consistently increased abundance of all the IPA-associated taxa across all RS-fed mice. In addition, major changes were observed for metabolites solely or primarily metabolized in the gut (e.g., trimethylamine-N-oxide), metabolites that have a significant entero-hepatic circulation (i.e., bile acids), lipid metabolites (e.g., cholesterol sulfate), metabolites indicating increased energy turnover (e.g., tricarboxylic acid cycle intermediates and ketone bodies), and increased antioxidants such as reduced glutathione. Our findings reveal potentially novel mediators of high microbiome-accessible carbohydrate-derived health benefits.-Koay,Y. C., Wali. J. A., Luk, A. W. S., Macia, L., Cogger, V. C., Pulpitel, T. J., Wahl, D., Solon-Biet, S. M., Holmes, A., Simpson, S. J., O'Sullivan, J. F. Ingestion of resistant starch by mice markedly increases microbiome-derived metabolites.