Excess dietary sugar impairs Drosophila adult stem cells via elevated reactive oxygen species-induced JNK signaling.

High-sugar diets (HSDs) often lead to obesity and type 2 diabetes, both metabolic syndromes associated with stem cell dysfunction. However, it is unclear whether excess dietary sugar affects stem cells. Here, we report that HSD impairs stem cell function in the intestine and ovaries of female Drosophila prior to the onset of insulin resistance, a hallmark of type 2 diabetes. Although 1 week of HSD leads to obesity, impaired oogenesis and altered lipid metabolism, insulin resistance does not occur. HSD increases glucose uptake by germline stem cells (GSCs) and triggers reactive oxygen species-induced JNK signaling, which reduces GSC proliferation. Removal of excess sugar from the diet reverses these HSD-induced phenomena. A similar phenomenon is found in intestinal stem cells (ISCs), except that HSD disrupts ISC maintenance and differentiation. Interestingly, tumor-like GSCs and ISCs are less responsive to HSD, which may be because of their dependence on glycolytic metabolism and high energy demand, respectively. This study suggests that excess dietary sugar induces oxidative stress and damages stem cells before insulin resistance develops, a mechanism that may also occur in higher organisms.

Age and an obesogenic diet affect mouse behaviour in a sex-dependent manner.

Obesity is rising globally and is associated with neurodevelopmental and psychiatric disorders among children, adolescents and young adults. Whether obesity is the cause or the consequence of these disorders remains unclear. To examine the behavioural effects of obesity systematically, locomotion, anxiety and social behaviour were assessed in male and female C57Bl/6J mice using the open field, elevated plus maze and social preference task. First, the effects of age and sex were examined in control mice, before investigating post-weaning consumption of a high fat-high sugar diet commonly consumed in human populations with high rates of obesity. In the open field and elevated plus maze, locomotor activity and anxiety-related behaviours reduced with aging in both sexes, but with different sex-specific profiles. The high fat-high sugar diet reduced food and calorie intake and increased body mass and fat deposition in both sexes. In the open field, both male and female mice on the obesogenic diet showed reduced locomotion; whereas, in the elevated plus maze, only females fed with the obesogenic diet displayed reduced anxiety-related behaviours. Both male and female mice on the obesogenic diet had a significantly higher social preference index than the control group. In conclusion, the findings demonstrate that the behavioural effects of age and diet-induced obesity all depend on the sex of the mouse. This emphasises the importance of considering the age of the animal and including both sexes when assessing behavioural phenotypes arising from dietary manipulations.

Metabolic mitochondrial alterations prevail in the female rat heart 8 weeks after exercise cessation.

BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.

Intergenerational effects of a paternal Western diet during adolescence on offspring gut microbiota, stress reactivity, and social behavior.

The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility.

Self-reported intake of high-fat and high-sugar diet is not associated with cognitive stability and flexibility in healthy men.

Animal studies indicate that a high-fat/high-sugar diet (HFS) can change dopamine signal transmission in the brain, which could promote maladaptive behavior and decision-making. Such diet-induced changes may also explain observed alterations in the dopamine system in human obesity. Genetic variants that modulate dopamine transmission have been proposed to render some individuals more prone to potential effects of HFS. The objective of this study was to investigate the association of HFS with dopamine-dependent cognition in humans and how genetic variations might modulate this potential association. Using a questionnaire assessing the self-reported consumption of high-fat/high-sugar foods, we investigated the association with diet by recruiting healthy young men that fall into the lower or upper end of that questionnaire (low fat/sugar group: LFS, n = 45; high fat/sugar group: HFS, n = 41) and explored the interaction of fat and sugar consumption with COMT Val158Met and Taq1A genotype. During functional magnetic resonance imaging (fMRI) scanning, male participants performed a working memory (WM) task that probes distractor-resistance and updating of WM representations. Logistic and linear regression models revealed no significant difference in WM performance between the two diet groups, nor an interaction with COMT Val158Met or Taq1A genotype. Neural activation in task-related brain areas also did not differ between diet groups. Independent of diet group, higher BMI was associated with lower overall accuracy on the WM task. This cross-sectional study does not provide evidence for diet-related differences in WM stability and flexibility in men, nor for a predisposition of COMT Val158Met or Taq1A genotype to the hypothesized detrimental effects of an HFS diet. Previously reported associations of BMI with WM seem to be independent of HFS intake in our male study sample.

Liver Oxidative Status, Serum Lipids Levels after Bariatric Surgery and High-Fat, High-Sugar Diet in Animal Model of Induced Obesity.

Nutritional status is a major determinant of hepatocyte injuries associated with changed metabolism and oxidative stress. This study aimed to determine the relations between oxidative stress, bariatric surgery, and a high-fat/high-sugar (HFS) diet in a diet-induced obesity rat model. Male rats were maintained on a control diet (CD) or high-fat/high-sugar diet (HFS) inducing obesity. After 8 weeks, the animals underwent SHAM (n = 14) or DJOS (n = 14) surgery and the diet was either changed or unchanged. Eight weeks after the surgeries, the activity of superoxide dismutase isoforms (total SOD, MnSOD, and CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and lutathione S-transferase, as well as the thiol groups (-SH) concentration, total antioxidant capacity (TAC), total oxidative stress (TOS) levels, and malondialdehyde (MDA) concentration liver tissue were assessed. The total cholesterol, triglycerides (TG), and high-density lipoprotein (HDL) concentrations were measured in the serum. The total SOD and GPX activities were higher in the SHAM-operated rats than in the DJOS-operated rats. The MnSOD activity was higher in the HFS/HFS than the CD/CD groups. Higher CuZnSOD, GST, GR activities, -SH, and MDA concentrations in the liver, and the triglyceride and cholesterol concentrations in the serum were observed in the SHAM-operated rats than in the DJOS-operated rats. The CAT activity was significantly higher in the HFS-fed rats. Lower TAC and higher TOS values were observed in the SHAM-operated rats. Unhealthy habits after bariatric surgery may be responsible for treatment failure and establishing an obesity condition with increased oxidative stress.

Early unhealthy eating habits underlie morpho-functional changes in the liver and adipose tissue in male rats.

Early-life consumption of high-fat and sugar-rich foods is recognized as a major contributor for the onset of metabolic dysfunction and its related disorders, including diabetes and nonalcoholic fatty liver disease. The lifelong impact of early unhealthy eating habits that start at younger ages remains unclear. Therefore, to better understand the effects of diet, it is essential to evaluate the structural and functional changes induced in metabolic organs and potential mechanisms underlying those changes. To investigate the long-term effects of eating habits, young male rats were exposed to high-sugar and high-energy diets. After 14 weeks, body composition was assessed, and histopathological changes were analyzed in the liver and adipose tissue. Serum biochemical parameters were also determined. Expression of inflammatory markers in the liver was evaluated by immunohistochemistry. Our results revealed that serum levels of glucose, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile were increased in rats red high-sugar and high-energy diets. Histopathological alterations were observed, including abnormal hepatocyte organization and lipid droplet accumulation in the liver, and abnormal structure of adipocytes. In both unhealthy diet groups, hepatic expression of Toll-like receptor 4 (TLR4), cyclooxygenase 2 (COX-2), and E-selectin were increased, as well as a biomarker of oxidative stress. Together, our data demonstrated that unhealthy diets induced functional and structural changes in the metabolic organs, suggesting that proinflammatory and oxidative stress mechanisms trigger the hepatic alterations and metabolic dysfunction.

Maternal high-sugar diet results in NMDA receptors abnormalities and cognitive impairment in rat offspring.

Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring. Behavioral studies have shown sex-related changes like impaired recognition memory in adolescent males and spatial memory in females. Molecular results confirmed an NMDA receptor hypofunction along with subunit composition abnormalities in the medial prefrontal cortex of adolescent offspring. In young adults, GluN2A-containing receptors were dominant in the medial prefrontal cortex, while in the hippocampus the GluN2B subunit contribution was elevated. In conclusion, we demonstrated that a maternal high-sugar diet can affect the memory processes in the offspring by disrupting the NMDA receptor composition and regulation in the medial prefrontal cortex and the hippocampus.

Metabolic imprinting induced by a high-sugar diet: effects on microRNA expression and insulin resistance in young rats.

BACKGROUND: Metabolic imprinting describes associations between nutritional experiences of early life and the development of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet (HSD) and its effects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the effects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. METHODS AND RESULTS: Weaned male Wistar rats (N = 6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-, or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometabolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N = 3). The HSD resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent effect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. CONCLUSIONS: MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with the improvement in IR observed after a 12-week HSD feeding period. This is the first time that excessive sugar intake post-weaning has been associated with miRNA production by rWAT with an impact on IR development.

Parental high-fat high-sugar diet programming and hypothalamus adipose tissue axis in male Wistar rats.

PURPOSE: Maternal nutrition during early development and paternal nutrition pre-conception can programme offspring health status. Hypothalamus adipose axis is a target of developmental programming, and paternal and maternal high-fat, high-sugar diet (HFS) may be an important factor that predisposes offspring to develop obesity later in life. This study aims to investigate Wistar rats' maternal and paternal HFS differential contribution on the development, adiposity, and hypothalamic inflammation in male offspring from weaning until adulthood. METHODS: Male progenitors were fed a control diet (CD) or HFS for 10 weeks before mating. After mating, dams were fed CD or HFS only during pregnancy and lactation. Forming the following male offspring groups: CD-maternal and paternal CD; MH-maternal HFS and paternal CD; PH-maternal CD and paternal HFS; PMH-maternal and paternal HFS. After weaning, male offspring were fed CD until adulthood. RESULTS: Maternal HFS diet increased weight, visceral adiposity, and serum total cholesterol levels, and decreased hypothalamic weight in weanling male rats. In adult male offspring, maternal HFS increased weight, glucose levels, and hypothalamic NFκBp65. Paternal HFS diet lowered hypothalamic insulin receptor levels in weanling offspring and glucose and insulin levels in adult offspring. The combined effects of maternal and paternal HFS diets increased triacylglycerol, leptin levels, and hypothalamic inflammation in weanling rats, and increased visceral adiposity in adulthood. CONCLUSION: Male offspring intake of CD diet after weaning reversed part of the effects of parental HFS diet during the perinatal period. However, maternal and paternal HFS diet affected adiposity and hypothalamic inflammation, which remained until adulthood.

Unhealthy Diets Induce Distinct and Regional Effects on Intestinal Inflammatory Signalling Pathways and Long-Lasting Metabolic Dysfunction in Rats.

The intestinal epithelium is a principal site for environmental agents' detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-κB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-κB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life.

N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats.

Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug-taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N-Acetylcysteine (NAC) is a cysteine pro-drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction-like behaviour towards highly palatable food in a rat model of diet-induced obesity. Adult male Sprague-Dawley rats were placed on a high-fat high-sugar diet for 8 weeks and then assigned to diet-induced obesity-prone (DIO) or diet-induced obesity-resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high-fat high-sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive-like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100 mg/kg, i.p.) for 14 days. By the end of the treatment period, lever-pressing by NAC-treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction-like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating.

Maternal high-sugar diet changes offspring vulnerability to reinstatement of cocaine-seeking behavior: Role of melanocortin-4 receptors.

Maternal diet significantly influences the proper development of offspring in utero. Modifications of diet composition may lead to metabolic and mental disorders that may predispose offspring to a substance use disorder. We assessed the impact of a maternal high-sugar diet (HSD, rich in sucrose) consumed during pregnancy and lactation on the offspring phenotype in the context of the rewarding and motivational effects of cocaine and changes within the central melanocortin (MC) system. Using an intravenous cocaine self-administration model, we showed that maternal HSD leads to increased relapse of cocaine-seeking behavior in male offspring. In addition, we demonstrated that cocaine induces changes in the level of MC-4 receptors in the offspring brain, and these changes depend on maternal diet. These studies also reveal that an MC-4 receptor antagonist reduces the reinstatement of cocaine-seeking behavior, and offspring exposed to maternal HSD are more sensitive to its effects than offspring exposed to the maternal control diet. Taken together, the results suggest that a maternal HSD and MC-4 receptors play an important role in cocaine relapse.

Addiction-like response in brain and behavior in a rat experimental model of night-eating syndrome.

STUDY OBJECTIVES: Individuals ailing from night eating syndrome (NES) consume more than 25% of their daily food intake during the normal sleep time, delaying their sleep or waking up in the middle of the night to eat. This study explored two experimental conditions resembling NES in Wistar rats by offering palatable food during the sleep phase, alone or combined with sleep delay. Also we explored their impact on addiction-like changes in the brain and behavior. METHODS: Experiment 1 explored the brain response after a first NES-like event; experiment 2 and 3 explored addiction-like behaviors c-Fos and FosB/ΔFosB in corticolimbic regions after 4 weeks exposition to NES-like conditions and after one week of withdrawal, respectively. For all 3 experiments 6 experimental groups were used: 1. Control; 2. Restricted access (1 h) to high-sugar diet (HSD) or to 3. high-fat diet (HFD); 4., Sleep delay for 4 h (SD) (from ZT0-ZT4, rats using slow rotating wheels); 5. SD + HSD; 6. SD + HFD. RESULTS: A first event of eating a palatable diet with or without SD was sufficient to stimulate c-Fos and ΔFosB. Along 4 weeks of exposure to the palatable diets rats exhibited escalation and binge eating, which was highest for the HFD. At this stage, SD did not influence behavioral changes nor the neuronal response. After one-week in withdrawal, rats exhibited craving and effort to obtain their palatable diet. The brains of rats previously exposed to sleep delay maintained high levels of FosB/ΔFosB in the accumbens shell and high c-Fos activation in the insular cortex. CONCLUSIONS: In our experimental models of NES-like a HFD in the sleep phase and SD are risk factors to develop binge eating and addiction-like behaviors.

Dietary Fat and Sugar Differentially Affect ß-Adrenergic Stimulation of Cardiac ERK and AKT Pathways in C57BL/6 Male Mice Subjected to High-Calorie Feeding.

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways. METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only. RESULTS: Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P < 0.001), induced glucose intolerance (P < 0.001), and increased insulin concentrations >1.5-fold (P < 0.05), thereby enhancing basal and ISO-stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+25-63%; P < 0.05). Compared with HFD, the high-sugar diets potentiated ISO-mediated stimulation of the glucose-sensitive kinases PYK2 (>47%; P < 0.05 for HCD and HSD) and ERK (>34%; P < 0.05 for WD, HCD, and HSD), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (>64%; P < 0.05 for WD, HCD, and HSD). CONCLUSIONS: Dietary fat and sugar affect cardiac growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological cardiac remodeling.

A high-sugar diet affects cellular and humoral immune responses in Drosophila.

A high-sugar diet (HSD) induces Type 2 diabetes (T2D) and obesity, which severely threaten human health. The Drosophila T2D model has been constructed to study the mechanisms of insulin resistance, diet-induced cardiovascular diseases and other conditions. Innate immunity is the first line of defense against invading pathogens and parasites. However, few studies have focused on the relationship between a HSD and the innate immune response in Drosophila. In this study, we fed flies a high-sucrose diet and observed defects in the phagocytosis of latex beads and B. bassiana spores. The actin cytoskeleton was also disrupted in hemocytes from HSD-fed larvae. Furthermore, HSD induced the differentiation of lamellocytes in the lymph gland and circulating hemolymph, which rarely occurs in healthy bodies, via JNK signaling. In addition, the Toll and JNK pathways were excessively activated in the fat bodies of HSD-fed larvae, and a large number of dead cells were observed. Finally, HSD induced the aberrant activation of the innate immune system, including inflammation. Our results have established a connection between T2D and the innate immune response.

Effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.

BACKGROUND: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys. METHODS: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment. RESULTS: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS. CONCLUSIONS: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

Obesity and Aging in the Drosophila Model.

Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity. Whereas obesity induced by high-fat or high-sugar diet is associated with hyperglycemia, cardiomyopathy, and in some cases, shortening of lifespan, there are also examples in which obesity correlates with longevity. Transgenic lines with downregulations of the insulin/insulin-like growth factor (IIS) and target of rapamycin (TOR) signaling pathways, flies reared under dietary restriction, and even certain longevity selection lines are obese, yet long-lived. The mechanisms that underlie the differential lifespans in distinct types of obesity remain to be elucidated, but fat turnover, inflammatory pathways, and dysregulations of glucose metabolism may play key roles. Altogether, Drosophila is an excellent model to study the physiology of adiposity in both health and disease.

High sugar diet disrupts gut homeostasis though JNK and STAT pathways in Drosophila.

The incidence of diseases associated with a high sugar diet has increased in the past years, and numerous studies have focused on the effect of high sugar intake on obesity and metabolic syndrome. However, how a high sugar diet influences gut homeostasis is still poorly understood. In this study, we used Drosophila melanogaster as a model organism and supplemented a culture medium with 1 M sucrose to create a high sugar condition. Our results indicate that a high sugar diet promoted differentiation of intestinal stem cells through upregulation of the JNK pathway and downregulation of the JAK/STAT pathway. Moreover, the number of commensal bacteria decreased in the high sugar group. Our data suggests that the high caloric diet disrupts gut homeostasis and highlights Drosophila as an ideal model system to explore gastrointestinal disease.

Diet, gut microbiota and cognition.

The consumption of a diet high in fat and sugar can lead to the development of obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive decline. In the human gut, the trillions of harmless microorganisms harboured in the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of a diet high in fat and sugar changes the healthy microbiota composition which leads to an imbalanced microbial population in the gut, a phenomenon known as "gut dysbiosis". It has been shown that certain types of gut microbiota are linked to the pathogenesis of obesity. In addition, long-term consumption of a high fat diet is associated with cognitive decline. It has recently been proposed that the gut microbiota is part of a mechanistic link between the consumption of a high fat diet and the impaired cognition of an individual, termed "microbiota-gut-brain axis". In this complex relationship between the gut, the brain and the gut microbiota, there are several types of gut microbiota and host mechanisms involved. Most of these mechanisms are still poorly understood. Therefore, this review comprehensively summarizes the current evidence from mainly in vivo (rodent and human) studies of the relationship between diet, gut microbiota and cognition. The possible mechanisms that the diet and the gut microbiota have on cognition are also presented and discussed.