Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development, Body Fat, and Lifespan.
ABSTRACT: Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients-carbohydrate, lipid, or protein-resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance.
Project description:Obesity and its comorbidities are a growing health epidemic. Interactions between genetic background, the environment, and behavior (i.e., diet) greatly influence organismal energy balance. Previously, we described obesogenic mutations in the gene Split ends (Spen) in Drosophila melanogaster, and roles for Spen in fat storage and metabolic state. Lipid catabolism is impaired in Spen-deficient fat storage cells, accompanied by a compensatory increase in glycolytic flux and protein catabolism. Here, we investigate gene-diet interactions to determine if diets supplemented with specific macronutrients can rescue metabolic dysfunction in Spen-depleted animals. We show that a high-yeast diet partially rescues adiposity and developmental defects. High sugar partially improves developmental timing as well as longevity of mated females. Gene-diet interactions were heavily influenced by developmental-stage-specific organismal needs: extra yeast provides benefits early in development (larval stages) but becomes detrimental in adulthood. High sugar confers benefits to Spen-depleted animals at both larval and adult stages, with the caveat of increased adiposity. A high-fat diet is detrimental according to all tested criteria, regardless of genotype. Whereas Spen depletion influenced phenotypic responses to supplemented diets, diet was the dominant factor in directing the whole-organism steady-state metabolome. Obesity is a complex disease of genetic, environmental, and behavioral inputs. Our results show that diet customization can ameliorate metabolic dysfunction underpinned by a genetic factor.
Project description:Although the role of individual macronutrients in the development of obesity remains controversial, changes in macronutrient composition of the diet may have played a causal role in the obesity epidemic. The aim of this analysis was to determine the percentage energy (%E) for protein, carbohydrate and fat of Australian adults' diets over time. Cross-sectional, national nutrition surveys from 1983, 1995 and 2012 assessed diet using one 24 h recall. The prevalence of obesity increased between each survey, from 9.6% to 19.7% and 27.7%. Protein (%E) differed between each survey and contributed 17.7%, 16.8% and 18.3% energy in 1983, 1995 and 2012, respectively (p < 0.001). Carbohydrate (%E) increased from 40.0% in 1983 to 44.9% in 1995 (p < 0.001), with no change in dietary fibre but declined in 2012 to 43.1%. Fat (%E) declined between each survey from 35.3%, 31.9%, to 30.9%, respectively (p < 0.001). Alcohol (%E) has declined for younger adults and men but intake increased for women aged >45 years. Prospective cohort studies with comprehensive assessment of foods consumed, together with measurements of weight and height, will advance the understanding of the relationship between macronutrients and changes in body weight and obesity.
Project description:The factors that distinguish metabolically healthy obesity from metabolically unhealthy obesity are not well understood. Diet has been implicated as a determinant of the unhealthy obesity phenotype, but which aspects of the diet induce dysmetabolism are unknown. The goal of this study was to investigate whether specific macronutrients or macronutrient combinations provoke dysmetabolism in the context of isocaloric, high-energy diets.Mice were fed 4 high-energy diets identical in calorie and nutrient content but different in nutrient composition for 3 weeks to 6 months. The test diets contained 42% carbohydrate (sucrose or starch) and 42% fat (oleate or palmitate). Weight and glucose tolerance were monitored; blood and tissues were collected for histology, gene expression, and immunophenotyping.Mice gained weight on all 4 test diets but differed significantly in other metabolic outcomes. Animals fed the starch-oleate diet developed more severe hepatic steatosis than those on other formulas. Stable isotope incorporation showed that the excess hepatic steatosis in starch-oleate-fed mice derived from exaggerated adipose tissue lipolysis. In these mice, adipose tissue lipolysis coincided with adipocyte necrosis and inflammation. Notably, the liver and adipose tissue abnormalities provoked by starch-oleate feeding were reproduced when mice were fed a mixed-nutrient Western diet with 42% carbohydrate and 42% fat.The macronutrient composition of the diet exerts a significant influence on metabolic outcome, independent of calories and nutrient proportions. Starch-oleate appears to cause hepatic steatosis by inducing progressive adipose tissue injury. Starch-oleate phenocopies the effect of a Western diet; consequently, it may provide clues to the mechanism whereby specific nutrients cause metabolically unhealthy obesity.
Project description:The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated.
Project description:The cardiovascular complications of obesity have prompted interest in dietary interventions to reduce weight, including low-carbohydrate diets that are generally high in protein and fat. However, little is known about the long-term effects of these diets on vascular health. We examined the cardiovascular effects of a low-carbohydrate, high-protein diet (LCHP) in the ApoE(-/-) mouse model of atherosclerosis and in a model of ischemia-induced neovascularization. Mice on a LCHP were compared with mice maintained on either the standard chow diet (SC) or the Western diet (WD) which contains comparable fat and cholesterol to the LCHP. LCHP-fed mice developed more aortic atherosclerosis and had an impaired ability to generate new vessels in response to tissue ischemia. These changes were not explained by alterations in serum cholesterol, inflammatory mediators or infiltrates, or oxidative stress. The LCHP diet substantially reduced the number of bone marrow and peripheral blood endothelial progenitor cells (EPCs), a marker of vascular regenerative capacity. EPCs from mice on a LCHP diet also manifest lower levels of activated (phosphorylated) Akt, a serine-threonine kinase important in EPC mobilization, proliferation, and survival. Taken together, these data demonstrate that in animal models LCHP diets have adverse vascular effects not reflected in serum markers and that nonlipid macronutrients can modulate vascular progenitor cells and pathophysiology.
Project description:Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.
Project description:Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC<sub>50</sub> for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.
Project description:Diets of high nutritional quality can aid in the prevention and management of malnutrition in hospitalized patients. This study evaluated the nutritional quality of hospital patient menus. At three large acute care hospitals in Ontario, Canada, 84 standard menus were evaluated, which included regular and carbohydrate-controlled diets and 3000 mg and 2000 mg sodium diets. Mean levels of calories, macronutrients and vitamins and minerals provided were calculated. Comparisons were made with the Dietary Reference Intakes (DRI) and Canada's Food Guide (CFG) recommendations. Calorie levels ranged from 1281 to 3007 kcal, with 45% of menus below 1600 kcal. Protein ranged from 49 to 159 g (0.9-1.1 g/kg/day). Energy and protein levels were highest in carbohydrate-controlled menus. All regular and carbohydrate-controlled menus provided macronutrients within the Acceptable Macronutrient Distribution Ranges. The proportion of regular diet menus meeting the DRIs: 0% for fiber; 7% for calcium; 57% for vitamin C; and 100% for iron. Compared to CFG recommended servings, 35% met vegetables and fruit and milk and alternatives, 11% met grain products and 8% met meat and alternatives. These data support the need for frequent monitoring and evaluation of menus, food procurement and menu planning policies and for sufficient resources to ensure menu quality.
Project description:Nutrition influences skin structure; however, a systematic investigation into how energy and macronutrients (protein, carbohydrate and fat) affects the skin has yet to be conducted. We evaluated the associations between macronutrients, energy intake and skin structure in mice fed 25 experimental diets and a control diet for 15 months using the Geometric Framework, a novel method of nutritional analysis. Skin structure was associated with the ratio of dietary macronutrients eaten, not energy intake, and the nature of the effect differed between the sexes. In males, skin structure was primarily associated with protein intake, whereas in females carbohydrate intake was the primary correlate. In both sexes, the dermis and subcutaneous fat thicknesses were inversely proportional. Subcutaneous fat thickness varied positively with fat intake, due to enlarged adipocytes rather than increased adipocyte number. We therefore demonstrated clear interactions between skin structure and macronutrient intakes, with the associations being sex-specific and dependent on dietary macronutrient balance.
Project description:<h4>Importance</h4>It is crucial to incorporate quality and types of carbohydrate and fat when investigating the associations of low-fat and low-carbohydrate diets with mortality.<h4>Objective</h4>To investigate the associations of low-carbohydrate and low-fat diets with total and cause-specific mortality among US adults.<h4>Design, setting, and participants</h4>This prospective cohort study used data from the US National Health and Nutrition Examination Survey from 1999 to 2014 from 37 233 adults 20 years or older with 24-hour dietary recall data. Data were analyzed from July 5 to August 27, 2019.<h4>Exposures</h4>Overall, unhealthy, and healthy low-carbohydrate-diet and low-fat-diet scores based on the percentage of energy as total and subtypes of carbohydrate, fat, and protein.<h4>Main outcomes and measures</h4>All-cause mortality from baseline until December 31, 2015, linked to National Death Index mortality data.<h4>Results</h4>A total of 37 233 US adults (mean [SD] age, 49.7 [18.3] years; 19 598 [52.6%] female) were included in the present analysis. During 297 768 person-years of follow-up, 4866 total deaths occurred. Overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. The multivariable-adjusted hazard ratios for total mortality per 20-percentile increase in dietary scores were 1.07 (95% CI, 1.02-1.11; P?=?.01 for trend) for unhealthy low-carbohydrate-diet score, 0.91 (95% CI, 0.87-0.95; P?<?.001 for trend) for healthy low-carbohydrate-diet score, 1.06 (95% CI, 1.01-1.12; P?=?.04 for trend) for unhealthy low-fat-diet score, and 0.89 (95% CI, 0.85-0.93; P?<?.001 for trend) for healthy low-fat-diet score. The associations remained similar in the stratification and sensitivity analyses.<h4>Conclusions and relevance</h4>In this study, overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. Unhealthy low-carbohydrate-diet and low-fat-diet scores were associated with higher total mortality, whereas healthy low-carbohydrate-diet and low-fat-diet scores were associated with lower total mortality. These findings suggest that the associations of low-carbohydrate and low-fat diets with mortality may depend on the quality and food sources of macronutrients.