High fat intake aggravates hyperlipidemia and suppresses fatty liver symptoms induced by a high-sucrose diet in rats.

Overconsumption of sucrose or fat is widely acknowledged as a prominent feature of unhealthy dietary patterns. Both factors commonly co-occur and are recognized as hallmarks of the Western diet, which is an important contributor to non-communicative diseases. In this study, we investigated the hazards of high sucrose or fat intake, either alone or in combination. Wistar rats were divided into four groups and fed a control starch diet, high-sucrose diet, high-fat diet, or high-sucrose/fat diet for 30 days. High fat intake increased body weight and visceral and subcutaneous adipose tissue weights. Both high-sucrose and -fat diets were associated with increased plasma triglyceride and glucose levels, and high sucrose also elevated plasma cholesterol levels. The combination of high sucrose and fat synergistically elevated plasma triglyceride levels. The high-sucrose diet increased liver weight and hepatic total lipid and triglyceride levels, whereas this increase was suppressed by the high-fat diet. The high sucrose increased the mRNA levels of hepatic genes involved in fatty acid synthesis and transport (ACLY, ACACA, FAS, ELOVL6, SCD1, SREBP1, and CD36), whereas the high fat suppressed the high sucrose-induced expression of these genes. We observed that high sucrose and fat contents differently exerted their effects on hyperlipidemia and fatty liver. Furthermore, high fat aggravated hyperlipidemia and suppressed fatty liver induced by high sucrose.

Intriguing hepatoprotective effects of sucrose on hepatocellular carcinoma pathogenesis.

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis.

Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice.

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice.

BACKGROUND: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD). RESULTS: C57BL/6 mice (5-6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. Bacteroidetes, Firmicutes, and Proteobacteria were highly abundant in C-HFD group, while the Verrucomicrobia, Saccharibacteria (TM7), Actinobacteria, and Tenericutes were more abundant in F-HFD group. Other taxa in C-HFD group included the Bacteroides, Odoribacter, Sutterella, Firmicutes bacterium (AF12), Anaeroplasma, Roseburia, and Parabacteroides distasonis. An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (Acaca), Fatty acid synthase (Fasn), Stearoyl-CoA desaturase-1 (Scd1), Elongation of long-chain fatty acids family member 6 (Elovl6), Peroxisome proliferator-activated receptor-gamma (Pparg) and cholesterol synthesis (ß-(hydroxy ß-methylglutaryl-CoA reductase (Hmgcr). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (CD36), Fatty acid binding protein-1 (Fabp1) and efflux (ATP-binding cassette G1 (Abcg1), Microsomal TG transfer protein (Mttp) in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (Tnfa), C-C motif chemokine ligand 2 (Ccl2), and Interleukin-12 (Il12), as well as a tendency for liver fibrosis. CONCLUSION: These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance.

Exercise protects the hypothalamus morphology from the deleterious effects of high sucrose diet consumption.

A growing body of evidence suggests that elevated sucrose intake may contribute to the development of neurological disorders. Recognizing that regular exercise has the potential to reduce the occurrence of neuromuscular disorders, the present research investigated the impact of exercise on the redox status of the hypothalamus in mitigating the adverse effects associated with high sucrose intake. Forty Wistar albino rats were subjected to a high sucrose diet, with some groups engaging in exercise for a duration of 3 months. The exercise regimen was found to sustain the redox balance in the hypothalamus. In summary, the consumption of a high sucrose diet resulted in the disturbance of the histological morphology of the hypothalamus, accompanied by an increased percentage of caspase-3 positive cells. Additionally, the high sucrose diet disrupted the oxidant/antioxidant ratio in favor of oxidants, leading to elevated levels of AOPPs and AGEP. Conversely, exercise was effective in restoring most of these values to levels approximating the control group, indicating a potential protective effect of regular exercise against the detrimental impacts of high sucrose dietary consumption on the hypothalamus. Graphical abstract.

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.

Differential effects of fish-oil and cocoa-butter based high-fat/high-sucrose diets on endocrine pancreas morphology and function in mice.

Introduction: A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice. Methods: C57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells. Results and discussion: Fish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas ß-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function.

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

BACKGROUND: Excessive 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. METHODS: We 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). RESULTS: The 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. CONCLUSIONS: Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.

Association between consumption of sweeteners and endometrial cancer risk: a systematic review and meta-analysis of observational studies.

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

High sucrose intake exacerbates airway inflammation through pathogenic Th2 and Th17 response in ovalbumin (OVA)-induced acute allergic asthma in C57BL/6 mice.

Asthma is an inflammatory disease characterized by chronic inflammation in lung tissues and excessive mucus production. High-fat diets have long been assumed to be a potential risk factor for asthma. However, to date, very few direct evidence indicating the involvement of high sucrose intake (HSI) in asthma progression exists. In this study, we investigate the effect of HSI on ovalbumin (OVA)-sensitized allergic asthma mice. We observed that HSI increased the expression of inflammatory genes (IL-1ß, IL-6, TNF-α) in adipose tissues and led to reactive oxygen species generation in the liver and lung. In addition, HSI accelerated the TLR4/NF-κB signaling pathway leading to MMP9 activation, which promotes the chemokines and TGF-ß secretion in the lungs of OVA-sensitized allergic asthma mice. More importantly, HSI significantly promoted the pathogenic Th2 and Th17 responses. The increase of IL-17A secretion by HSI increased the expression of chemokines (MCP-1, CXCL1, CXCL5, CXCL8). It resulted in eosinophil and mast cell infiltration in the lung and trachea. We also demonstrated that HSI increased mucus hypersecretion, which was validated by increased main mucin protein (MUC5AC) secreted in the lungs. Our findings suggest that HSI exacerbates the development of Th2/Th17-predominant asthma by upregulating the TLR4-mediated NF-κB pathway, leading to excessive MMP9 production.

Elderly rats fed with a high-fat high-sucrose diet developed sex-dependent metabolic syndrome regardless of long-term metformin and liraglutide treatment.

Aim/Introduction: The study aimed to determine the effectiveness of early antidiabetic therapy in reversing metabolic changes caused by high-fat and high-sucrose diet (HFHSD) in both sexes. Methods: Elderly Sprague-Dawley rats, 45 weeks old, were randomized into four groups: a control group fed on the standard diet (STD), one group fed the HFHSD, and two groups fed the HFHSD along with long-term treatment of either metformin (HFHSD+M) or liraglutide (HFHSD+L). Antidiabetic treatment started 5 weeks after the introduction of the diet and lasted 13 weeks until the animals were 64 weeks old. Results: Unexpectedly, HFHSD-fed animals did not gain weight but underwent significant metabolic changes. Both antidiabetic treatments produced sex-specific effects, but neither prevented the onset of prediabetes nor diabetes. Conclusion: Liraglutide vested benefits to liver and skeletal muscle tissue in males but induced signs of insulin resistance in females.

Relationship of cardiac remodeling and perfusion alteration with hepatic lipid metabolism in a prediabetic high fat high sucrose diet female rat model.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is known to be linked with metabolic associated fatty liver disease and type 2 diabetes, but few studies assessed this relationship in prediabetes, especially among women, who are at greater risk of CVD. We aimed to evaluate cardiac alterations and its relationship with hepatic lipid metabolism in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS). METHODS AND RESULTS: Wistar female rats were divided into 2 groups fed for 5 months with standard or HFS diet. We analyzed cardiac morphology, function, perfusion and fibrosis by Magnetic Resonance Imaging. Hepatic lipid contents along with inflammation and lipid metabolism gene expression were assessed. Five months of HFS diet induced glucose intolerance (p < 0.05), cardiac remodeling characterized by increased left-ventricular volume, wall thickness and mass (p < 0.05). No significant differences were found in left-ventricular ejection fraction and cardiac fibrosis but increased myocardial perfusion (p < 0.01) and reduced cardiac index (p < 0.05) were shown. HFS diet induced hepatic lipid accumulation with increased total lipid mass (p < 0.001) and triglyceride contents (p < 0.05), but also increased mitochondrial (CPT1a, MCAD; (p < 0.001; p < 0.05) and peroxisomal (ACO, LCAD; (p < 0.05; p < 0.001) ß-oxidation gene expression. Myocardial wall thickness and perfusion were correlated with hepatic ß-oxidation genes expression. Furthermore, myocardial perfusion was also correlated with hepatic lipid content and glucose intolerance. CONCLUSION: This study brings new insights on the relationship between cardiac sub-clinical alterations and hepatic metabolism in female prediabetic rats. Further studies are warranted to explore its involvement in the higher CVD risk observed among prediabetic women.

High-Sucrose Diet Accelerates Arthritis Progression in a Collagen-Induced Rheumatoid Arthritis Model.

SCOPE: High dietary sugar and sweeteners are suspected to cause the development of rheumatoid arthritis (RA) symptoms through the induction of proinflammatory cytokine release. However, the mechanisms by which increased dietary sugar affects RA etiology are not yet fully understood. The study uses a mouse model of collagen-induced RA (CIA) to investigate the relationship between excessive sugar consumption and RA risk. METHODS AND RESULTS: RA-associated pathological features are assessed in the nonimmunized (NI) control group, the CIA-positive control group, and the CIA + high-sucrose diet (CIA+HS, 63% calories from sucrose) group. Compared with the CIA group, the CIA+HS group shows a greater increase in paw thickness and clinical scores, as well as, a higher degree of pannus formation and inflammation in the knee, ankle, and sole tissues. Moreover, the infiltration of immune cells is increased in the CIA+HS group. Although the expression of hepatic lipogenic genes, is not altered, that of toll-like receptor (TLR4) and IL-1ß is considerably elevated in the CIA+HS group. CONCLUSIONS: These findings suggest that excessive sucrose consumption causes hepatic fibrosis and inflammation, contributing to the pathophysiology of RA.

Alterations in skeletal muscle morphology and mechanics in juvenile male Sprague Dawley rats exposed to a high-fat high-sucrose diet.

Although once a health concern largely considered in adults, the obesity epidemic is now prevalent in pediatric populations. While detrimental effects on skeletal muscle function have been seen in adulthood, the effects of obesity on skeletal muscle function in childhood is not clearly understood. The purpose of this study was to determine if the consumption of a high-fat high-sucrose (HFS) diet, starting in the post-weaning period, leads to changes in skeletal muscle morphology and mechanics after 14 weeks on the HFS diet. Eighteen 3-week-old male CD-Sprague Dawley rats were randomly assigned to a HFS (C-HFS, n = 10) or standard chow diet (C-CHOW, n = 8). Outcome measures included: weekly energy intake, activity levels, oxygen consumption, body mass, body composition, metabolic profile, serum protein levels, and medial gastrocnemius gene expression, morphology, and mechanics. The main findings from this study were that C-HFS rats: (1) had a greater body mass and percent body fat than control rats; (2) showed early signs of metabolic syndrome; (3) demonstrated potential impairment in muscle remodeling; (4) produced lower relative muscle force; and (5) had a shift in the force-length relationship, indicating that the medial gastrocnemius had shorter muscle fiber lengths compared to those of C-CHOW rats. Based on the results of this study, we conclude that exposure to a HFS diet led to increased body mass, body fat percentage, and early signs of metabolic syndrome, resulting in functional deficits in MG of childhood rats.

Intake of Artificial Sweeteners by Children: Boon or Bane?

BACKGROUND: Sugar is the main culprit in many health dysfunctions. Excessive sugar intake can negatively affect oral health, precipitate diabetes, and lead to weight gain and obesity. Sucrose is the primary form of sugar, and is strongly correlated with dental caries. Artificial sweeteners are chemically synthesized sugar substitutes that are generally regarded as being low-calorie. OBJECTIVE: This review examines the current evidence in the literature for the need for artificial sweeteners and outlines its implications for the health of children. We briefly outline its adverse effects, and concerns regarding their safety. REVIEW RESULTS: Artificial sweeteners are a widely used food additive. Six main artificial sweeteners are approved by the food and drug administration (FDA). The conflicting results and divergent regulatory norms of each sweetener are a constant cause of concern and debate. However, most studies have spotlighted the beneficial effects of artificial sweeteners. Dental caries diminish with the increase in sweetener intake. An increase in appetite and eventually weight gain is observed in individuals consuming artificial sweeteners. CONCLUSION: Artificial sweeteners are indeed a bane according to present studies, although more research on recently discovered non-nutritive artificial sweeteners is required. It also has a positive effect on overall health disorders. If one curbs the onset of dental caries, then the eventual rise is highly unlikely. CLINICAL SIGNIFICANCE: Artificial sweeteners' effect on lowering dental caries will help to reduce the caries index in general. Oral hygiene is maintained, and the growth of oral bacterium is depressed. Research on novel sweeteners will help to compare their efficacy in caries prevention compared to existing ones. It is necessary to educate people on artificial sweeteners and its implication as one can use them by being aware of their properties.

A high-sucrose diet causes microbiota composition shift and promotes the susceptibility of mice to Salmonella Typhimurium infection.

A westernized diet characterized by high fat and sugar is tightly associated with the development of metabolic diseases and inflammatory bowel disease. Although a high-fat diet has been extensively studied for its involvement in various diseases, fewer studies have examined the impact of a high-sugar diet on the development of certain diseases, particularly enteric infections. This study aimed to explore the effect of a high sucrose diet on Salmonella Typhimurium-induced infection. C57BL/6 mice received a normal diet (Control) or a high sucrose diet (HSD) for eight weeks and then were infected by Salmonella Typhimurium. The high-sugar diet profoundly altered the relative abundance of certain microbial taxa. Bacteroidetes and Verrucomicrobiota were more abundant in normal diet-fed mice than in HSD-fed mice. Moreover, short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were significantly higher in mice from the control group than the HSD group. More S. Typhimurium counts in feces and other tissues were observed in HSD-fed mice after infection. Tight junction proteins and antimicrobial peptides were significantly decreased in HSD-fed mice. Fecal microbiota transplantation (FMT) demonstrated that mice that received normal fecal microbiota had lower Salmonella Typhimurium burdens compared with mice that received HSD fecal microbiota, indicating that the altered microbial communities are associated with the severity of infection. Together, these findings suggest that the excessive intake of sucrose disturbs intestinal homeostasis and predisposes mice to Salmonella-induced infection.

Gestational Exercise Antagonises the Impact of Maternal High-Fat High-Sucrose Diet on Liver Mitochondrial Alterations and Quality Control Signalling in Male Offspring.

Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are relevant modulators of the intrauterine environment, increasing the risk of liver metabolic alterations in mothers and offspring. In contrast, as a non-pharmacological approach against metabolic disorders, exercise is highly recommended in GDM treatment. We analysed whether gestational exercise (GE) protects mothers from diet-induced GDM metabolic consequences and mitigates liver mitochondrial deleterious alterations in their 6-week-old male offspring. Female Sprague Dawley rats were fed with control or high-fat high-sucrose (HFHS) diet and kept sedentary or submitted to GE. Male offspring were sedentary and fed with control diet. Sedentary HFHS mothers and their offspring showed impaired hepatic mitochondrial biogenesis and morphological evidence of mitochondrial remodelling. In contrast, GE-related beneficial effects were demonstrated by upregulation of mitochondrial biogenesis signalling markers and mitochondrial fusion proteins and downregulation of mitochondrial fission protein. Alterations in miR-34a, miR-130b, and miR-494, associated with epigenetic regulation of mitochondrial biogenesis, suggested that GE is a more critical modulator of intergenerational changes in miRs expression than the maternal diet. Our data showed that GE positively modulated the altered hepatic mitochondrial biogenesis and dynamics markers and quality control signalling associated with maternal HFHS-diet-related GDM in mothers and offspring.

Sugar-sweetened beverages exacerbate high-fat diet-induced inflammatory bowel disease by altering the gut microbiome.

High-fat diets (HFDs) and frequent consumption of sugar-sweetened beverages (SSBs) are potential contributors to increasing inflammatory bowel disease (IBD) incidences. While HFDs have been implicated in mild intestinal inflammation, the role of sucrose in SSBs remains unclear. Therefore, we studied the role of SSBs in IBD pathogenesis in a mouse model and humans. C57BL6/J mice were given ad libitum access to a sucrose solution or plain water for 10 weeks, with or without an HFD. Interestingly, sucrose solution consumption alone did not induce gut inflammation in mice; however, when combined with an HFD, it dramatically increased the inflammation score, submucosal edema, and CD45+ cell infiltration. 16S ribosomal RNA gene-sequencing revealed that sucrose solution and HFD co-consumption significantly increased the relative abundance of IBD-related pathogenic bacteria when compared with HFD consumption. RNA sequencing and flow cytometry showed that co-consumption promoted pro-inflammatory cytokine and chemokine synthesis, dendritic-cell expansion, and IFN-γ+TNF-α+CD4+ and CD8+ T-cell activation. Fecal microbiota transplantation from HFD- and sucrose water-fed mice into gut-sterilized mice increased the susceptibility to dextran sulfate sodium-induced colitis in the recipient mice. Consistent herewith, high consumption of SSBs and animal fat-rich diets markedly increased systemic inflammation-associated IBD marker expression in humans. In conclusion, SSBs exacerbate HFD-induced colitis by triggering a shift of the gut microbiome into a pathobiome. Our findings provide new insights for the development of strategies aimed at preventing IBD.

Impact of dietary sucralose and sucrose-sweetened water intake on lipid and glucose metabolism in male mice.

AIMS: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. MATERIALS AND METHODS: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. RESULTS: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. CONCLUSION: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.