High-sucrose Diet Research Articles

Promoting mitochondrial dynamics by inhibiting the PINK1-PRKN pathway to relieve diabetic nephropathy.

Diabetes is a metabolic disorder characterized by high blood glucose levels and is a leading cause of kidney disease. Diabetic nephropathy has been attributed to dysfunctional mitochondria. However, many questions remain about the exact mechanism. The structure, function and molecular pathways are highly conserved between mammalian podocytes and Drosophila nephrocytes; therefore, we used flies on a high-sucrose diet to model type 2 diabetic nephropathy. The nephrocytes from flies on a high-sucrose diet showed a significant functional decline and decreased cell size, associated with a shortened lifespan. Structurally, the nephrocyte filtration structure, known as the slit diaphragm, was disorganized. At the cellular level, we found altered mitochondrial dynamics and dysfunctional mitochondria. Regulating mitochondrial dynamics by either genetic modification of the Pink1-Park (mammalian PINK1-PRKN) pathway or treatment with BGP-15, mitigated the mitochondrial defects and nephrocyte functional decline. These findings support a role for Pink1-Park-mediated mitophagy and associated control of mitochondrial dynamics in diabetic nephropathy, and demonstrate that targeting this pathway might provide therapeutic benefits for type 2 diabetic nephropathy.

Overexpression of Slc22a18 facilitates fat accumulation in mice

We previously reported that solute carrier family 22 member 18 (Slc22a18) regulates lipid accumulation in 3T3-L1 adipocytes. Here, we provide additional evidence derived from experiments with adenoviral vector expression and genetic manipulation of mice. In primary cultured rat hepatocytes, adenoviral overexpression of mouse Slc22a18 increased triglyceride accumulation and triglyceride synthetic activity, which was decreased in an adenoviral knockdown experiment. Adenoviral overexpression of mouse Slc22a18 in vivo caused massive fatty liver in mice, even under normal dietary conditions. Conversely, adenoviral knockdown of mouse Slc22a18 reduced hepatic lipid accumulation induced by a high-glucose and high-sucrose diet. We created Slc22a18 knockout mice, which grew normally and showed no obvious spontaneous phenotypes. However, compared with control littermates, the knockout mice exhibited decreased hepatic triglyceride content under refeeding conditions, significantly reduced epididymal fat mass, and tended to have lower liver weight in conjunction with leptin deficiency. Finally, we created transgenic mice overexpressing rat Slc22a18 in an adipose-specific manner, which had increased body weight and epididymal fat mass primarily because of increased adipocyte cell volume. In these transgenic mice, a positive correlation was observed between adiposity and the expression levels of the rat Slc22a18 transgene. Taken together, these results indicate that Slc22a18 has positive effects on lipid accumulation in vivo.

Voluntary Wheel Running Reduces Cardiometabolic Risks in Female Offspring Exposed to Lifelong High-Fat, High-Sucrose Diet.

Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. Dams were fed either an HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 wk before pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 wk of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed ( n = 10), LFLS/Ex ( n = 5), HFHS/Sed ( n = 6), HFHS/Ex ( n = 5). Cardiac function was assessed at 25 wk, with tissue collection at 26 wk for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. Although maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding postweaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspring mitigated these effects, aligning more with LFLS/Sed offspring. Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks.

Detection of typical indigenous gut bacteria related to kanpyo Lagenaria siceraria var. hispida powder in murine caecum and human faecal cultures.

Kanpyo (KP) is an edible dried product produced by peeling the fruit of the gourd Lagenaria siceraria var. hispida; it is used in the traditional Japanese cuisine. The health functionality of KP due to its rich dietary fibre is expected to include a possible combined effect of KP-responsive indigenous gut bacteria (KP-RIB). However, its effect on the gut microbiota is unclear. To determine the effects of the KP on the gut microbiota and their host, Institute of Cancer Research mice were fed a high-sucrose diet containing no fibre (NF) or 5% (w/w) KP for 14days, and their caecal microbiota was analysed by 16S rRNA (V4) amplicon sequencing. Higher faecal frequency and weight and lower spleen weight and spleen tumour necrosis factor-α levels were observed in KP-fed mice than in NF-fed mice (p < 0.05). KP increased and decreased the abundance of short-chain fatty acid producer Lachnospiraceae and obesity-inflammation related Allobaculum species, respectively. In the case of human faecal cultures, stool samples from five healthy volunteers were inoculated and incubated at 37°C for 24h anaerobically; 3.2% (w/v) KP suppressed putrefactive compounds (indole, phenol, and ammonia). KP increased butyrate-producer Faecalibacterium, acetate/lactate-producer Bifidobacterium, and Lachnospira. Furthermore, KP cultures showed high antioxidant and RAW264.7 macrophage cell activation capacities. These results suggest that KP-RIB and KP intake may synergistically affect host health. However, further studies are required to clarify the synergistic effects of KP and KP-RIB.

Tocotrienols Prevent the Decline of Learning Ability in High-Fat, High-Sucrose Diet-Fed C57BL/6 Mice.

Obesity has been increasing worldwide and is well-known as a risk factor for cognitive decline. It has been reported that oxidative stress in the brain is deeply involved in cognitive dysfunction in rodent models. While there are many studies on oxidation in the liver and adipose tissue of obese mice, the relationship between obesity-induced cognitive dysfunction and brain oxidation has not been elucidated. Here, we show that obesity induced by a high-fat, high-sucrose diet (HFSD) alters cognitive function in C57BL/6 male mice, and it may involve the acceleration of brain oxidation. Tocotrienols (T3s), which are members of the vitamin E family, can prevent HFSD-induced cognitive changes. To elucidate these mechanisms, respiratory metabolism, locomotor activity, temperature around brown adipose tissue, and protein profiles in the cerebrum cortex were measured. Contrary to our expectation, respiratory metabolism was decreased, and temperature around brown adipose tissue was increased in the feeding of HFSD. The proteins that regulate redox balance did not significantly change, but 12 proteins, which were changed by HFSD feeding and not changed by T3s-treated HFSD compared to control mice, were identified. Our results indicated that HFSD-induced obesity decreases mouse learning ability and that T3s prevent its change. Additionally, feeding of HFSD significantly increased brain oxidation. However, further study is needed to elucidate the mechanisms of change in oxidative stress in the brain by obesity.

Exacerbated ischemia-reperfusion injury in fatty livers is mediated by lipid peroxidation stress and ferroptosis

BackgroundIschemia-reperfusion injury is a common problem in liver surgery and transplantation. Although ischemia-reperfusion injury is known to be more pronounced in fatty livers, the underlying mechanisms for this difference remain poorly understood. We hypothesized that ferroptosis plays a significant role in fatty liver ischemia-reperfusion injury due to increased lipid peroxidation in the presence of stored iron in the fatty liver. To test this hypothesis, the ferroptosis pathway was evaluated in a murine fatty liver ischemia-reperfusion injury model. MethodsC57BL6 mice were fed with a normal diet or a high fat, high sucrose diet for 12 weeks. At 22 weeks of age, liver ischemia-reperfusion injury was induced through partial (70%) hepatic pedicle clamping for 60 minutes, followed by 24 hours of reperfusion before tissue harvest. Acyl–coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal were quantified in the liver tissues. In separate experiments, liproxstatin-1 or vehicle control was administered for 7 consecutive days before liver ischemia-reperfusion injury. ResultsExacerbated ischemia-reperfusion injury was observed in the livers of high fat, high sucrose diet fed mice. High fat, high sucrose diet + ischemia-reperfusion injury (HDF+IRI) livers had a significantly greater abundance of acyl–coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal compared with normal diet + ischemia-reperfusion injury (ND+IRI) livers or sham fatty livers, which indicated an increase of ferroptosis. HFD fed animals receiving liproxstatin-1 injections had a significant reduction in serum aspartate transaminase and alanine transaminase after ischemia-reperfusion injury, consistent with attenuation of ischemia-reperfusion injury in the liver. ConclusionFerroptosis plays a significant role in ischemia-reperfusion injury in fatty livers. Inhibiting ferroptotic pathways in the liver may serve as a novel therapeutic strategy to protect the fatty liver in the setting of ischemia-reperfusion injury.

The anti-hyperlipidemia effect of Atractylodes macrocephala Rhizome increased HDL via reverse cholesterol transfer

AimAtractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. MethodsSD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. ResultsAMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. ConclusionThe main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Cyclocarya paliurus leaves alleviate high-sucrose diet-induced obesity by improving intestinal metabolic disorders.

High-sucrose diets are common in daily life but harmful to human health. Cyclocarya paliurus leaves (CPL) are a kind of tea used to alleviate metabolic diseases and are widely used in China. However, the effects of CPL on high-sucrose-induced obesity are unknown. This study aimed to describe the changes in gut metabolism induced by a high-sucrose diet and to reveal the potential mechanisms through which CPL alleviate high-sucrose diet-induced obesity. A high-sucrose-induced obesity model was generated in C57BL/6J and KM mice. The effects of CPL on obese mice were evaluated, and changes in the gut microbiota and intestinal metabolites induced by CPL treatment were observed. Furthermore, the fecal microbiota transplantation (FMT) method was used to prove that the effects of CPL on high-sucrose induced obesity depend on the changes of gut microbiota. The results of the C57BL/6J mouse experiment revealed that high-sucrose intake induced fat deposition and altered the gut microbiota. CPL treatment decreased fat deposition and alleviated disorders of the gut microbiota. Furthermore, CPL treatment increased the utilization of amnio acids, long fatty acids and saccharides and produced more bile acids, indole derivatives and less trimethylamine (TMA). A confirmatory experiment in KM mice also revealed that CPL can alleviate obesity, ameliorate intestinal metabolic disorders, and upregulate the expression of tight junction proteins in the intestinal mucosa. These results demonstrated that CPL could prevent high sucrose-induced obesity and generate more beneficial intestinal microbial metabolites but less harmful intestinal microbial metabolites.

A Cross-Sectional Quantitative Metabolomics Study Evidencing the Metabolic Signature in Six Organs during a 14-Week High-Fat High-Sucrose and Standard Diet in Mice.

Obesity is a risk factor for many diseases, such as type 2 diabetes and cardiovascular diseases. In line with the need for precision medicine, the search for biomarkers reporting the progression of obesity- and diet-associated disorders is urgent. We used NMR to determine the metabolomics profile of key organs (lung, liver, heart, skeletal muscle, kidney, and brain) and serum from male C57Bl/6J mice (5 weeks old) fed for 6, 10, and 14 weeks on a high-fat and high-sucrose diet (HFHSD) vs. a standard diet (STD). We determined metabolite concentrations in the organs at each time point, which allowed us to discriminate age- and diet-related effects as well as the interactions between both, highlighting the need to evaluate the influence of age as a confounding factor on metabolic signatures. Notably, the analysis revealed the influence of time on metabolite concentrations in the STD condition, probably reflecting the juvenile-to-adult transition. Variations impacted the liver and lung metabolites, revealing the strong influence of the HFHS diet on normal metabolism maturation during youth.

VCD-induced menopause mouse model reveals reprogramming of hepatic metabolism

ObjectiveMenopause adversely impacts systemic energy metabolism and increases the risk of metabolic disease(s) including hepatic steatosis, but the mechanisms are largely unknown. Dosing female mice with vinyl cyclohexene dioxide (VCD) selectively causes follicular atresia in ovaries, leading to a murine menopause-like phenotype. MethodsIn this study, we treated female C57BL6/J mice with VCD (160 mg/kg i.p. for 20 consecutive days followed by verification of the lack of estrous cycling) to investigate changes in body composition, energy expenditure (EE), hepatic mitochondrial function, and hepatic steatosis across different dietary conditions. ResultsVCD treatment induced ovarian follicular loss and increased follicle-stimulating hormone (FSH) levels in female mice, mimicking a menopause-like phenotype. VCD treatment did not affect body composition, or EE in mice on a low-fat diet (LFD) or in response to a short-term (1-week) high-fat, high sucrose diet (HFHS). However, the transition to a HFHS lowered cage activity in VCD mice. A chronic HFHS diet (16 weeks) significantly increased weight gain, fat mass, and hepatic steatosis in VCD-treated mice compared to HFHS-fed controls. In the liver, VCD mice showed suppressed hepatic mitochondrial respiration on LFD, while chronic HFHS resulted in compensatory increases in hepatic mitochondrial respiration. Also, liver RNA sequencing revealed that VCD promoted global upregulation of hepatic lipid/cholesterol synthesis pathways. ConclusionOur findings suggest that the VCD-induced menopause model compromises hepatic mitochondrial function and lipid/cholesterol homeostasis that sets the stage for HFHS diet-induced steatosis while also increasing susceptibility to obesity.

Blighia welwitschii (Hiern) leaf solvent fractions ameliorate diabetes in Drosophila melanogaster induced by high–sucrose diet

The therapeutic potential of Blighia welwitschii in insulin resistant disorder is poorly understood. Herein, the antioxidant and anti-diabetes potentials of solvent fractions of B. welwitschii leaf was performed using various experimental approaches in Drosophila melanogaster model. In vitro antioxidant and alpha amylase inhibitory assay were carried out on successive fractions of aqueous, butanol, ethylacetate and hexane using standard procedures. The most active fraction was subjected to HPLC analysis and the bioactive compounds identified were virtually screened against D. melanogaster α-amylase (2QV4) binding site using Schrodinger suite (2017 v 1). The butanol and ethylacetate fractions were fed to diabetes and non-diabetes flies to study their anti-diabetes and anti-oxidant properties followed by ILP-2, InR and IMPL2 mRNA expression using standard procedures. The findings from this study showed that, ethylacetate and butanol fractions possess high percentage hydroxyl radical inhibiting capacity and appreciable ferric reducing antioxidant potential. The phenolics and flavonoids contents were appreciably high compared with other fractions. These fractions also restored glucose imbalance and thiol homeostasis in diabetes flies. The in silico and in vitro anti-diabetes analyses suggested that, the active compounds possess inhibitory efficacy against α-amylase with cyanidin-3-o-rutinoside having the highest binding affinity (−12.8 kcal/mol). The EBW showed non-significant down-regulation of IMPL2 and InR mRNA expression in diabetes flies compared with diabetes untreated flies. Overall, butanol and ethylacetate fractions of B. welwitschii leaf ameliorate insulin resistant diabetes and therefore might be useful for the management of diabetes. However, further anti-diabetes study in other animal model is proposed to compliment this finding.

ACAD10 is not required for metformin's metabolic actions or for maintenance of whole-body metabolism in C57BL/6J mice.

Acyl-coenzyme A dehydrogenase family member 10 (ACAD10) is a mitochondrial protein purported to be involved in the fatty acid oxidation pathway. Metformin is the most prescribed therapy for type 2 diabetes; however, its precise mechanisms of action(s) are still being uncovered. Upregulation of ACAD10 is a requirement for metformin's ability to inhibit growth in cancer cells and extend lifespan in Caenorhabditis elegans. However, it is unknown whether ACAD10 plays a role in metformin's metabolic actions. We assessed the role for ACAD10 on whole-body metabolism and metformin action by generating ACAD10KO mice on a C57BL/6J background via CRISPR-Cas9 technology. In-depth metabolic phenotyping was conducted in both sexes on a normal chow and high fat-high sucrose diet. Compared with wildtype mice, we detected no difference in body composition, energy expenditure or glucose tolerance in male or female ACAD10KO mice, on a chow diet or high-fat, high-sucrose diet (p ≥ .05). Hepatic mitochondrial function and insulin signalling was not different between genotypes under basal or insulin-stimulated conditions (p ≥ .05). Glucose excursions following acute administration of metformin before a glucose tolerance test were not different between genotypes nor was body composition or energy expenditure altered after 4 weeks of daily metformin treatment (p ≥ .05). Despite the lack of a metabolic phenotype, liver lipidomic analysis suggests ACAD10 depletion influences the abundance of specific ceramide species containing very long chain fatty acids, while metformin treatment altered clusters of cholesterol ester, plasmalogen, phosphatidylcholine and ceramide species. Loss of ACAD10 does not alter whole-body metabolism or impact the acute or chronic metabolic actions of metformin in this model.

High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures

BackgroundExcessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear.MethodsWe established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS).ResultsThe HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures.ConclusionsOur results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.

Taraxacum officinale Extracts Alleviate Anhedonia and Depression by Inhibiting UPRmt and Mitophagy in the Hippocampi of T2DM Rats

<i>Taraxacum officinale</i> Extracts Alleviate Anhedonia and Depression by Inhibiting UPR^mt and Mitophagy in the Hippocampi of T2DM Rats

Активність ензимів поліольного шляху у нирках щурів за умов різної забезпеченості раціону протеїном і сахарозою

The study examined the activity of enzymes in the polyol pathway and the status of free radical processes in the kidneys of rats subjected to different dietary protein and sucrose levels. It was found that the kidneys of animals consuming a highsucrose diet, irrespective of protein content, exhibited the highest increase in the activity of polyol pathway enzymes, namely aldose reductase and sorbitol dehydrogenase. Consumption of a high-sucrose diet enhances the generation of O2 •- in the kidneys by almost twofold, and hydroxyl radical by over fourfold compared to control indicators. This is accompanied by a twofold increase in the content of TBARS-active products and a threefold increase in the content of carbonyl derivatives of proteins, against the background of a decrease in the content of free thiol groups in proteins. The pronounced generation of hydroxyl radicals, accumulation of TBARS-active products, and reduction in the content of free SH-groups in proteins are characteristic of animals that consumed a high-sucrose diet in the context of dietary protein deficiency. It has been demonstrated that excessive sucrose consumption is a critical factor, influencing the activity of enzymes in the polyol pathway and the intensity of free radical processes. The obtained results may be considered as predisposing factors for disruptions in the structural and functional organization of the kidneys under conditions of nutrient imbalance.

Effects of Sichuan pepper (huājiāo) powder on disease activity and caecal microbiota of dextran sodium sulphate-induced inflammatory bowel disease mouse model.

Sichuan pepper [Zanthoxylum bungeanum; huājiāo (HJ)] is a widely used spice in China and has better antioxidative, anti-glycation, and bile acid-lowering properties than cumin and coriander seeds. HJ affects inflammation-related cytokines and caecal microbiota in mice fed a low-fibre and high-sucrose diet. To determine the ameliorative effect of HJ on inflammatory bowel disease, C57BL/6 mice were divided into three groups and fed distilled water (control) or 3% (w/v) dextran sodium sulphate (DSS) in drinking water with normal chow containing 0% or 5% (w/w) HJ powder for seven days. After 6 days of feeding, diarrhoea, decreased body weight, and blood in faeces were observed in the DSS group. DSS treatment increased the spleen weight and damaged the colon tissue. These inflammatory indices were inhibited by HJ treatment. Amplicon sequencing of the 16S rDNA (V4) gene of the caecal content revealed a decrease in the alpha diversity (Simpson index D) in the DSS treatment group compared to the control group. The abundance of caecal Desulfovibrio, an inflammation-related genus, was higher and the caecal Lachnospiraceae and Bacteroides levels were lower in the DSS-treated mice than those in the control mice. However, HJ suppressed the DSS-induced changes in the caecal microbiota. HJ intake contributes to the reduction in inflammation and maintenance of the gut microbiota. However, the strong antioxidant properties of phenolic compounds and fermentability of water-soluble dietary fibres in HJ and their relationship with other functional properties warrant further investigation.

Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum.

The regular intake of diets high in saturated fat and sugars increases oxidative stress and has been linked to cognitive decline and premature brain aging. The cerebellum is highly vulnerable to oxidative stress and thus, obesogenic diets might be particularly detrimental to this tissue. However, the precise molecular mechanisms behind obesity-related brain damage are still not clear. Since protein carbonylation, a biomarker of oxidative stress, influences protein functions and is involved in metabolic control, the current investigation addressed the effect of long-term high-fat and high-sucrose diet intake on the cerebellum of Sprague-Dawley rats by deciphering the changes caused in the carbonylated proteome. The antioxidant effects of fish oil supplementation on cerebellar carbonylated proteins were also investigated. Lipid peroxidation products and carbonylated proteins were identified and quantified using immunoassays and 2D-LC-MS/MS in the cerebellum. After 21 weeks of nutritional intervention, the obesogenic diet selectively increased carbonylation of the proteins that participate in ATP homeostasis and glutamate metabolism in the cerebellum. Moreover, the data demonstrated that fish oil supplementation restrained carbonylation of the main protein targets oxidatively damaged by the obesogenic diet, and additionally protected against carbonylation of several other proteins involved in amino acid biosynthesis and neurotransmission. Therefore, dietary interventions with fish oils could help the cerebellum to be more resilient to oxidative damage. The results could shed some light on the effect of high-fat and high-sucrose diets on redox homeostasis in the cerebellum and boost the development of antioxidant-based nutritional interventions to improve cerebellum health.

High-sugar diet leads to loss of beneficial probiotics in housefly larvae guts.

The housefly (Musca domestica) is a common insect species with only a few recurrent bacterial taxa in its gut microbiota, because the numerous microbial acquisition routes in its septic habitats can favor transient microbes. Here, we investigated the role of the diet on the microbiota and the developmental success of a housefly strain reared on three substrates. We used a control wheat bran-based substrate, and added clotted cream and sucrose to make a high-fat, and a high-sugar substrate, respectively. The conducted survey revealed that, in contrast to the high-fat diet, the high-sugar diet caused lower developmental success and less diverse microbiota, in which several lactobacilli were replaced with Weissella bacterial phylotypes. Cultures with sucrose as the sole carbon source confirmed that a Weissela confusa strain, isolated from larvae, could utilize sucrose more efficiently than other tested lactic acid bacteria; a result also supported by gene function prediction analysis. Enhancing the rearing substrate with Limosilactobacillus fermentum and Lactiplantibacillus plantarum strains, which were isolated from control larvae, could not only revert the negative effect of the high-sucrose diet on development, but also increase the gut bacterial diversity. In our study, we show that the microbiota shifts in response to the high-sucrose diet did not benefit the host, that showed lower developmental success. In contrast, high-sucrose favored specific components of the microbiota, that continued to be enriched even after multiple generations, outcompeting beneficial bacteria. Also, microbiome manipulation showed the potential of probiotics to rescue host performance and restore the microbiome.

Intestinal Morphology and Glucose Transporter Gene Expression under a Chronic Intake of High Sucrose.

Sucrose is a disaccharide that is degraded into fructose and glucose in the small intestine. High-sucrose and high-fructose diets have been reported, using two-dimensional imaging, to alter the intestinal morphology and the expression of genes associated with sugar transport, such as sodium glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5). However, it remains unclear how high-fructose and high-sucrose diets affect the expression of sugar transporters and the intestinal morphology in the whole intestine. We investigate the influence of a chronic high-sucrose diet on the expression of the genes associated with sugar transport as well as its effects on the intestinal morphology using 3D imaging. High sucrose was found to increase GLUT2 and GLUT5 mRNA levels without significant changes in the intestinal morphology using 3D imaging. On the other hand, the delay in sucrose absorption by an α-glucosidase inhibitor significantly improved the intestinal morphology and the expression levels of SGLT1, GLUT2, and GLUT5 mRNA in the distal small intestine to levels similar to those in the proximal small intestine, thereby improving glycemic control after both glucose and sucrose loading. These results reveal the effects of chronic high-sugar exposure on glucose absorption and changes in the intestinal morphology.

Cross-sectional association between blood cholesterol and calcium levels in genetically diverse strains of mice.

Genetically diverse outbred mice allow for the study of genetic variation in the context of high dietary and environmental control. Using a machine learning approach, we investigated clinical and morphometric factors that associate with serum cholesterol levels in 840 genetically unique Diversity Outbred mice of both sexes (n = 417 male and 423 female), and on both acontrol chow (% kcals in diet: protein 22%, carbohydrate 62%, fat 16%,no cholesterol) and high fat high sucrose (%kcals in diet: protein 15%, carbohydrate 41%, fat 45%, 0.05% cholesterol). We find expected elevations of cholesterol in male mice, as well as in mice with elevated serum triglycerides and/or fed a high fat high sucrose diet. The third strongest predictor was serum calcium which correlated with serum cholesterol across both diets and sexes (r = 0.39-0.48) in both Diversity Outbred (P = 3.0 × 10-43 ) and BXD (P = 0.005) mice. This is in-line with several human cohort studies which show associations between calcium and cholesterol, and calcium as an independent predictor of cardiovascular events.