Both Maternal High-Fat and Post-Weaning High-Carbohydrate Diets Increase Rates of Spontaneous Hepatocellular Carcinoma in Aged-Mouse Offspring
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ABSTRACT:
SUBMITTER: Holt D
PROVIDER: S-EPMC11357072 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:Obesity remains prevalent in the US. One potential treatment is vagus nerve stimulation (VNS), which activates the sensory afferents innervating the stomach that convey stomach volume and establish satiety. However, current VNS approaches and stimulus optimization could benefit from additional understanding of the underlying neural response to stomach distension. In this study, obesity-prone Sprague Dawley rats consumed a standard, high-carbohydrate, or high-fat diet for several months, leading to diet-induced obesity in the latter two groups. Under anesthesia, the neural activity in the vagus nerve was recorded with a penetrating microelectrode array while the stomach was distended with an implanted balloon. Vagal tone during distension was compared to baseline tone prior to distension. Responses were strongly correlated with stomach distension, but the sensitivity to distension was significantly lower in animals that had been fed the nonstandard diets. The results indicate that both high fat and high carbohydrate diets impair vagus activity.
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Project description:Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.
| S-EPMC11343608 | biostudies-literature
Project description:UnlabelledLow-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets.MethodsMale Wistar rats were fed a standard control diet ad libitum or pair-fed isoenergetic amounts of three experimental diets for 4 weeks. The diets had the following macronutrient composition (% metabolizable energy: carbohydrates, fat, protein): control (64.3/16.7/19), LC-HF-low protein (LC-HF-LP, 1.7/92.8/5.5), LC-HF-normal-protein (LC-HF-NP, 2.2/78.7/19.1), and a high fat diet with carbohydrates ("high fat", 19.4/61.9/18.7).ResultsBody weight gain was reduced in all pair-fed experimental groups as compared to rats fed the control diet, with more pronounced effect in rats on LC-HF diets than on the high fat diet with carbohydrates. High fat diets increased expression of PGC1α and ADRB3 in BAT indicating higher SNS outflow. However, UCP1 mRNA expression and expression of UCP1 assessed by immunohistochemistry was not different between diet groups. In accordance, analysis of mitochondrial function in-vitro by extracellular flux analyser (Seahorse Bioscience) and measurement of inducible thermogenesis in vivo (primary endpoint), explored by indirect calorimetry following norepinephrine injection, did not show significant differences between groups. Histology of BAT revealed increased lipid droplet size in rats fed the high-fat diet and both LC-HF diets.ConclusionAll experimental diets upregulated expression of genes which are indicative for increased BAT activity. However, the functional measurements in vivo revealed no increase of inducible BAT thermogenesis. This indicates that lower body weight gain with LC-HF diets and a high fat diet in a pair-feeding setting is not caused by increased adaptive thermogenesis in BAT.
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Project description:Prenatal ethanol exposure (PEE) is an established risk factor for intrauterine growth retardation. The present study was designed to determine whether PEE can increase the susceptibility of high-fat diet (HFD)-induced metabolic syndrome (MS) in adult offspring in a sex-specific manner, based on a generalized linear model analysis. Pregnant Wistar rats were administered ethanol (4 g/kg.d) from gestational day 11 until term delivery. All offspring were fed either a normal diet or a HFD after weaning and were sacrificed at postnatal week 20, and blood samples were collected. Results showed that PEE reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels but enhanced serum glucose, insulin, insulin resistant index (IRI), triglyceride and total cholesterol (TC) concentrations. Moreover, the analysis showed interactions among PEE, HFD and sex. In the PEE offspring, HFD aggravated the decrease in ACTH and corticosterone levels and further increased serum glucose, insulin, triglyceride and TC levels. The changes of serum ACTH, glucose and IRI levels in the female HFD rats were greater than those in the male HFD rats. Our findings suggest that PEE enhances the susceptibility to MS induced by HFD in a sex-specific manner, which might be primarily associated with the neuroendocrine metabolic programming by PEE.
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Project description:Previous studies demonstrated that diet-induced obese mice fed a semi-purified high-fat diet (HFD) had greater liver tumorigenesis than mice fed a non-semi-purified diet. Because ingredients present in standard unpurified diets may elicit potential chemopreventive properties that are not present in semi-purified diets, the present study evaluated hepatic tumorigenic effects of dietary fat by replacing it with refined carbohydrates [digestible saccharides; high-carbohydrate diet (HCD)] in a semi-purified diet without altering other components. Two-wk-old C57Bl/6J male mice were randomly injected i.p. with either the liver-specific carcinogen diethylnitrosamine (25 mg/kg body weight) to induce liver cancer or saline as the nontumor control. At age 6 wk, mice with or without cancer initiation were further randomly assigned to an HFD (26% and 60% energy from carbohydrates and fat, respectively) or an HCD (66% and 12% energy from carbohydrates and fat, respectively) and consumed food ad libitum for 24 wk. Results showed that HCD-fed mice had a comparable degree of hepatic tumorigenesis (tumor number and volume) as HFD-fed mice, despite having significantly reduced body weights. HCD feeding induced greater hepatic endoplasmic reticulum (ER) stress-mediated protein kinase RNA-activated-like kinase (PERK) activation and oncogenic interleukin-6/signal transducer and activator of transcription 3 signaling than HFD feeding. HCD-stimulated PERK signaling was associated with elevated expression of prosurvival markers in tumors, including induced protein kinase B activation, increased extracellular signal-regulated kinases 1/2 phosphorylation, and elevated cyclin D1 protein expression. However, HCD-mediated PERK activation in tumors was also positively associated with markers of proapoptosis, which included elevated CCAAT/enhancer-binding protein homology protein expression and increased cleaved caspase-3. HCD-fed mice had greater severity in hepatic steatosis than HFD-fed mice. HCD-induced steatosis exacerbation was associated with increased expression in hepatic de novo lipogenic markers that can promote ER stress. Together, these data indicated that chronic HCD consumption by mice can produce comparable severity of hepatic tumorigenesis as HFD consumption, potentially through upregulating PERK-mediated ER stress.
| S-EPMC3985820 | biostudies-other
Project description:BackgroundDietary patterns which exclude whole food groups, such as vegetarian, vegan and low carbohydrate high fat diet (LCHF), are increasingly popular in general public. When carefully planned, all these diets have some known benefits for health, but concerns are also raised in particular for LCHF. The quality of LCHF diet which individuals follow in real life without supervision is not known.MethodsOne hundred thirty healthy individuals with stable body mass following LCHF, vegan, vegetarian and omnivorous diet for at least six months, were compared in a cross-sectional study. Diet was analyzed through 3-day food records and FFQ, anthropometric measurements were performed and serum metabolic biomarkers determined from fasting blood.ResultsParticipants on LCHF diet had the intakes of micronutrients comparable to other groups, while the intakes of macronutrients differed in line with the definition of each diet. The intakes of saturated fats, cholesterol and animal proteins were significantly higher and the intakes of sugars and dietary fibers were lower compared to other groups. Healthy eating index 2015 in this group was the lowest. There were no differences in the levels of glucose, triacylglycerols and CRP among groups. Total and LDL cholesterol levels were significantly higher in LCHF group, in particular in participants with higher ketogenic ratio. Fatty acids intakes and intakes of cholesterol, dietary fibers and animal proteins explained 40% of variance in total cholesterol level, with saturated fatty acids being the strongest positive predictor and monounsaturated fatty acids a negative predictor.ConclusionNone of the self-advised diets provided all the necessary nutrients in optimal levels. Due to the detected increased levels of serum cholesterols, selection of healthy fat sources, higher intake of dietary fibers and partial replacing of animal sources with plant sources of foods should be recommended to the individuals selecting LCFH dietary pattern.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04347213.
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Project description:Aggressive interactions, and their consequences, are the most important causes of poor welfare in piglets. Aggressive behaviour can be modulated by the prenatal and neonatal environment in several species. Commercially kept pregnant sows are often subjected to food restriction, which can compromise their welfare. Limited information is available on the consequences of sow hunger during pregnancy on welfare outcomes for their piglets. High fibre diets can mitigate the feeling of hunger and, consequently, it may improve welfare and productivity measures. The aim of this study was to assess the consequences of feeding pregnant gilts with high fibre diets (HFD) on agonistic behaviour, as manifested by skin lesions, and indicators of fear in their piglets at weaning. Twenty-two pregnant gilts were fed either HFD, 12.86% of crude fibre, 2.4 kg per day (N = 14), or low fibre diet (LFD), 2.53% of crude fibre, 2.0 kg per day (N = 8). During lactation, both treatments received the same diet, ad libitum. We investigated the impact of HFD on behaviour and performance measures (birth weight, average daily gain, weaning weight, see S3 File) in the offspring. Skin lesions were evaluated before and after weaning in 156 piglets (100 HFD and 56 LFD), and 142 piglets were subjected to an open field test and a novel object test (87 HFD and 55 LFD). We found no treatment effect on the performance measures. Piglets born from gilts that received HFD had fewer skin lesions before weaning (D28) than the offspring of LFD gilts, while no difference was found during days 29 and 30. In the open field and novel object tests, there was no treatment effect on the behaviour of piglets. The improved skin health at weaning in piglets of sows fed HFD suggests less agonistic interactions amongst these littermates than in piglets of sows fed LFD.
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