Post-weaning High-fat Diet Research Articles

Protective Effect of Tertiary Butylhydroquinone against Obesity-induced Skeletal Muscle Pathology in Post-weaning High Fat Diet Fed Rats.

Obesity deleteriously affects skeletal muscle functionality starting from infancy to adulthood, leading to dysfunctional skeletal muscle. This study, therefore, evaluated the protective action of tert-butylhydroquinone (tBHQ) against obesity-induced skeletal muscle pathology in high-fat diet (HFD) fed rats. Twenty post-weaning male albino rats were randomized into four groups of five rats each as: Group 1 (control), Group 2 (HFD), Group 3 (orlistat) and Group 4 (tBHQ). Group one received rat pellets for 12 weeks, while groups 2 to 4 received HFD for 12 weeks. At the end of week 8, obesity was confirmed with Lee Obesity Index and body mass index values of ≥ 303 and ≥ 0.68 gcm2, respectively. Group 3 was given oral administration of orlistat (10 mg/kg, once daily), while group 4 was given oral administration of tBHQ (25 mg/kg, once daily). Administration of orlistat and tBHQ commenced from week 9 to the end of the experiment. Chronic exposure of post-weaning rats to HFD led to their development of the metabolic syndrome phenotypes in adulthood, characterized by obesity, hyperglycemia, dyslipidaemia, hyperinsulinaemia, insulin resistance as well as induction of oxidative stress and alteration of skeletal muscle markers, which were mitigated following supplementation with orlistat and tBHQ. The study showed the anti-obesity potentials of tBHQ and its protective action against HFD obesity-induced skeletal muscular pathology.

Sexual dimorphism in thermogenic regulators and metrnl expression in adipose tissue of offspring mice exposed to maternal and postnatal overnutrition.

Current study investigated the impact of maternaland postnatal overnutrition on phenotype of adipose, in relation to offspring thermogenesis and sex. Female C57BL/6J mice were fed with CHOW or high fat diet (HFD) for 2weeks before mating, throughout gestation and lactation. At weaning, pups were fed to 9weeks old with CHOW or HFD, which resulted in four groups for each gender--male or female: CHOW-CHOW (CC), CHOW-HFD (CH), HFD-CHOW (HC), HFD-HFD (HH). Maternal and post-weaning HFD enhanced thermogenic factors such as Acox1, Dio2 and Cox8b in iBAT of male and female offspring, but increased SIRT1, PGC-1α and UCP1 only in female. However, Acox1, Dio2 and Cox8b mRNA expression and SIRT1, PGC-1α and UCP1 protein expression were only enhanced upon maternal and post-weaning HFD in sWAT and pWAT of female offspring. Increased metrnl expression in adipose were observed in sex- and depot-specific manner, while enhanced circulating metrnl level was only observed in male offspring undergoing maternal HFD. Palmitic acid changed metrnl expression during preadipocytes differentiation and siRNA-mediated knockdown of metrnl inhibited preadipocyte differentiation. Female offspring were more prone to resist adverse outcomes induced by maternal and post-weaning overnutrition, which probably related to metrnl expression and thermogenesis.

Maternal low-protein diet alters hepatic lipid accumulation and gene expression related to glucose metabolism in young adult mouse offspring fed a postweaning high-fat diet

Maternal consumption of low-protein (LP) diet during pregnancy has been demonstrated to increase the chances of adult offspring developing metabolic syndrome, and this risk can be exacerbated when the postnatal diets do not align with the prenatal conditions. However, in our previous study, focusing on serum parameters and gene expression patterns within adipose tissue, we discovered the presence of “healthy obesity” in young adult offspring from dams that were fed an LP, as a response to a postweaning high-fat (HF) diet. Here, we subsequently investigated the role played by the liver and skeletal muscle in alleviation of insulin resistance in male offspring that were fed either control (C/C group) or HF diet (C/HF and LP/HF groups) for 22 weeks. While a postweaning HF diet increased liver weight and hepatic triglyceride (TG) and cholesterol levels in offspring of control dams, these levels were lower in the LP/HF group compared to the C/HF group. Analysis of the liver transcriptome identified 430 differentially expressed genes (DEGs) in the LP/HF and C/HF comparison. Especially, downregulated DEGs were enriched in carbohydrate metabolism and the levels of DEGs were significantly correlated with the levels of markers for serum glucose homeostasis and hepatic lipid accumulation. In the LP/HF group compared to the C/HF group, there was a decrease in the gastrocnemius muscle weight, while no differences were observed in gene expression levels associated with muscle fiber phenotype, mitochondrial function, and inflammation. In conclusion, maternal LP diet induced changes in lipid and glucose metabolism within the liver, similar to what was observed in adipose tissue, while there were no alterations in metabolic functions in the skeletal muscle in young offspring mice fed an HF diet. Further research that investigating the enduring impact of nutritional transition on offspring is essential to gain a comprehensive grasp of developmental programming throughout their entire lifespan.

Leucine supplementation in maternal high-fat diet alleviated adiposity and glucose intolerance of adult mice offspring fed a postweaning high-fat diet

BackgroundCombined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated.MethodsFemale mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring.ResultsHFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator‐activated receptor‐γ co‐activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring.ConclusionsLeucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

Large artery stiffening and mortality in a rat model of early vascular remodeling induced by intrauterine growth restriction and a high-fat diet.

Intrauterine growth restriction (IUGR) and exposure to a high-fat diet (HFD) independently increase the risk of cardiovascular disease (CVD) and hyperlipidemia. In our previous studies, IUGR increased blood pressure and promoted vascular remodeling and stiffness in early life, a finding that persisted and was augmented by a maternal HFD through postnatal day (PND) 60. The impact of these findings with aging and the development of hyperlipidemia and atherosclerosis remain unknown. We hypothesized that the previously noted impact of IUGR on hypertension, vascular remodeling, and hyperlipidemia would persist. Adult female rats were fed either a regular diet (RD) or high fat diet (HFD) prior to conception through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either RD or HFD through PND 365. For both control (C) and IUGR (I) and rats, this resulted in the following six groups per sex: offspring from RD dams weaned to an RD (CRR and IRR), or offspring from HFD dams weaned to either an RD (CHR and IHR) or to an HFD (CHH and IHH). IHH male and female rats had increased large artery stiffness, a suggestion of fatty streaks in the aorta, and persistent decreased elastin and increased collagen in the aorta and carotid arteries. Post-weaning HFD intake increased blood lipids regardless of IUGR status. IUGR increased HFD-induced mortality. We speculate that HFD-induced risk of CVD and mortality is potentiated by developmental programming of the ECM.

Voluntary Exercise Eliminates Maternal Gestational Hypertension-Induced Hypertensive Response Sensitization to Postweaning High-Fat Diet in Male Adult Offspring.

Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. The present study tested whether voluntary exercise would protect male offspring against maternal gestational hypertension-induced hypertensive response sensitization elicited by post-weaning high-fat diet (HFD). On low-lard-fat diet, offspring of both normotensive and hypertensive dams had comparable resting blood pressure, but HFD feeding elicited an enhanced increase in blood pressure (ie, hypertensive response sensitization) in sedentary offspring of hypertensive dams when compared with sedentary offspring of normotensive dams. The HFD fed sedentary offspring of hypertensive dams displayed greater sympathetic activity, enhanced pressor responses to centrally administered ANG II (angiotensin II) or leptin, and greater mRNA expression of proinflammatory cytokines, leptin, and a marker of blood-brain barrier leakage in the hypothalamic paraventricular nucleus. The enhanced blood pressure and central sympathetic activity in HFD-fed sedentary offspring of hypertensive dams were significantly reduced by exercise but fell only to levels comparable to HFD-fed exercising offspring of normotensive dams. HFD-induced increases in plasma IL-6 (interleukin-6) and sympathetic activity and greater pressor responses to central TNF (tumor necrosis factor)-α in offspring from both normotensive and hypertensive dams were also maintained after exercise. Nevertheless, exercise had remarkably beneficial effects on metabolic and autonomic function, brain reactivity to ANG II and leptin and gene expression of brain prohypertensive factors in all offspring. Voluntary exercise plays a beneficial role in preventing maternal hypertension-induced hypertensive response sensitization, and that this is associated with attenuation of enhanced brain reactivity and centrally driven sympathetic activity.

Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring.

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.

Effects of whole-life exposure to low-dose cadmium with post-weaning high-fat diet on offspring testes in a male mouse model

Although several studies have reported testicular impairments caused by cadmium (Cd) or obesity alone, the combined effect of Cd and obesity on the testes and its underlying mechanism remains unclear. We examined the combined effect of whole-life exposure to low-dose Cd started at preconception and post-weaning high-fat diet (HFD) on the testes of offspring mice. At weaning, male offspring parented with and without exposure to low-dose Cd were continued on the same drinking water regimen as their parents and fed with either a normal diet (ND) or HFD for 10 or 24 weeks. Whole-life exposure to Cd resulted in its accumulation in testes, and HFD induced obesity and lipid metabolism disorder. Exposure to Cd or HFD alone significantly decreased Johnsen scores, disrupted testicular structure, and increased germ cell apoptosis at both 10 and 24 weeks. However, co-exposure to Cd and HFD did not induce the toxic effects that were induced by either alone, as revealed by preserved testicular structure and spermatogenesis, lack of significant apoptosis, and increased cell proliferation. Mechanistically, the combined effects of low-dose Cd and HFD consumption were associated with the activation of the JAK/STAT pathway. These findings suggest that co-exposure to low-dose Cd and HFD did not cause Cd- or HFD-induced testicular injury, probably because of the activation of the JAK/STAT pathway to prevent germ cell apoptosis.

Sex-Specific Effects of Maternal and Post-Weaning High-Fat Diet on Adipose Tissue Remodeling and Asprosin Expression in Mice Offspring.

Perinatal high-fat diet (HFD) increases risk of metabolic disorders in offspring. Adipose tissue remodeling is associated with metabolic syndrome. The current study characterizes the profile of maternal HFD-induced changes in adipose tissue remodeling and adipokines expression in mice offspring. Female C57BL/6 mice are fed with CHOW or HFD for 2 weeks before mating, throughout gestation and lactation. At weaning, pups are randomly fed with CHOW or HFD, resulting in eight groups according to sex and maternal diet: Male CHOW-CHOW (MCC), Male CHOW-HFD (MCH), Male HFD-CHOW (MHC), Male HFD-HFD (MHH), Female CHOW-CHOW (FCC), Female CHOW-HFD (FCH), Female HFD-CHOW (FHC), and Female HFD-HFD (FHH). Increased body weight, impaired glucose tolerance, increased adipose tissue mass and hypertrophy, and decreased circulating asprosin level are only observed in male offspring exposure to maternal HFD. Serum asprosin level negatively correlates with fasting blood glucose, serum cholesterol (CHO), and high-density lipoprotein (HDL) levels, while positively correlates with serum low-density lipoprotein (LDL) and glutamate-oxaloacetate transaminase (GOT) levels in male offspring. A combination of genetic and biochemical analyses of adipokines shows the depot- and sex-specific changes in response to maternal and/or post-weaning HFD. This study's results reveal the differential metabolic changes in response to maternal and/or post-weaning HFD in male and female offspring. The effect of maternal HFD on metabolic phonotype is more obvious in male offspring, supporting the notion that males are more susceptible to HFD-induced metabolic disorders.

The role of CD36-Fabp4-PPAR\u03b3 in skeletal muscle involves insulin resistance in intrauterine growth retardation mice with catch-up growth

BackgroundStudies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society.MethodsThe pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes.ResultsAfter dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05).ConclusionsLBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.

Synergism between maternal and offspring high fat diet feeding in the non-human primate neuroactive metabolome

The microbiome produces small molecules, including neuroactive metabolites crucial for normal lifelong behavior. In a non-human primate (NHP) model, offspring exposed to maternal high fat diet (mHFD) display physiological changes compared to offspring exposed to maternal control diet (mCTR). To investigate the relationship between maternal diet and offspring post-weaning diet, we hypothesized that mHFD exposure plus a post-weaning high fat diet (HFD) will produce a persistently altered gut metabolome profile in vivo compared to mCTR exposure.

Deletion of Npas2 in the liver alters the functional gut microbiome at light/dark timepoints

In utero exposure of a maternal high fat diet (mHFD) results in the targeted epigenetic reprograming and disruption of circadian clock genes in the fetal liver. However, it is unclear if this disruption of the circadian clock exacerbates the effect of the offspring’s post-weaning high fat diet (oHFD) on the function of its gut microbiome. To understand the interaction of the circadian clock and the offspring gut microbiome with HFD feeding, we disrupted liver Npas2 expression and analyzed the resultant microbiome in light and dark cycles of feeding.

Lactational High Fat Diet in Mice Causes Insulin Resistance and NAFLD in Male Offspring Which Is Partially Rescued by Maternal Metformin Treatment.

Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD.

Sex differences in the effects of whole-life, low-dose cadmium exposure on postweaning high-fat diet-induced cardiac pathogeneses

We previously showed the development of cardiac remodeling (hypertrophy or fibrosis) in mice with either post-weaning high-fat diet (HFD, 60% kcal fat) feeding or exposure to chronic low-dose cadmium. Here, we determined whether whole-life exposure to environmentally relevant, low-dose cadmium affects the susceptibility of offspring to post-weaning HFD-induced cardiac pathologies and function. Besides, we also determined whether these effects are sex-dependent. Male and female mice were exposed to cadmium-containing (0, 0.5, or 5 parts per million [ppm]) drinking water before breeding; the pregnant mice and dams with offspring continually drank the same cadmium-containing water. After weaning, the offspring were continued on the same regime as their parents and fed either a HFD or normal fat diet for 24 weeks. Cardiac function was examined with echocardiography. Cardiac tissues were used for the histopathological and biochemical (gene and protein expression by real-time PCR and Western blotting) assays. Results showed a dose-dependent cadmium accumulation in the hearts of male and female mice along with decreased cardiac zinc and copper levels only in female offspring. Exposure to 5 ppm, but not 0.5 ppm, cadmium significantly enhanced HFD cardiac effects only in female mice, shown by worsened cardiac systolic and diastolic dysfunction (ejection fraction, mitral E-to-annular e′ ratio), increased fibrosis (collagen, fibronectin, collagen1A1), hypertrophy (cardiomyocyte size, atrial natriuretic peptide, β-myosin heavy chain), and inflammation (intercellular adhesion molecule-1, tumor necrosis factor-α, plasminogen activator inhibitor type 1), compared to the HFD group. These synergistic effects were associated with activation of the p38 mitogen-activated protein kinases (MAPK) signaling pathway and increased oxidative stress, shown by 3-nitrotyrosine and malondialdehyde, along with decreased metallothionein expression. These results suggest that whole-life 5 ppm cadmium exposure significantly increases the susceptibility of female offspring to HFD-induced cardiac remodeling and dysfunction. The underlying mechanism and potential intervention will be further explored in the future.

Abstract P194: Voluntary Exercise Eliminates Maternal Gestational Hypertension-induced Hypertensive Response Sensitization (htrs) In Post-weaning High Fat Diet Fed Male Adult Offspring

Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. Our previous studies demonstrated that maternal gestational hypertension (MGHT) induces hypertensive response sensitization (HTRS) elicited by post-weaning high fat diet (HFD) in male offspring. The present study tested whether voluntary exercise would protect against MGHT-induced HTRS in HFD fed male offspring. Male offspring from both normotensive (NT) and MGHT dams were given access to either “blocked” (sedentary offspring) or functional running (exercised offspring) wheels for 10 weeks during normal fat diet (NFD) or HFD feeding. HFD feeding significantly increased resting blood pressure (BP) in sedentary offspring of both NT (112.3±0.7 to 119.9±1.2 mmHg, p&lt;0.05) and MGHT (112.5±0.9 to 129.6±1.0 mmHg, p&lt;0.05) dams, but the elevated BP induced by HFD was greater in sedentary offspring of MGHT dams (129.6±1.0 vs. 119.9±1.2 mmHg, p&lt;0.05). The sedentary offspring of MGHT dams also displayed greater sympathetic tone and enhanced pressor responses to centrally administrated angiotensin (ANG) II or leptin. The running distance was comparable in four groups of exercise offspring (9.183±1.183, 9.192±1.677, 7.233±1.080, 8.482±1.455 kilometers/day, p&gt;0.05). Voluntary exercise did not alter BP in NFD fed offspring and HFD fed offspring of NT dams, but it attenuated BP in HFD fed offspring of MGHT dams (129.6±1.0 to 121.1±0.8 mmHg, p&lt;0.05) and body weight and heart rate in all offspring. Moreover, voluntary exercise significantly reduced sympathetic tone (Hexamethonium, ip, MAP Δ-50.6±1.0 to Δ-29.7±2.7 mmHg, p&lt;0.05) and pressor responses to central ANG II and leptin in HFD fed offspring of both NT (ANG II: Δ16.0±0.9 to Δ7.5±1.1 mmHg; leptin: Δ11.8±0.6 to Δ5.4±0.9 mmHg, p&lt;0.05) and MGHT (ANG II: Δ24.3±2.1 to Δ7.6±1.8 mmHg; leptin: Δ16.8±0.9 to Δ5.2±1.0 mmHg, p&lt;0.05) dams and eliminated the differences in these responses between NFD fed offspring and HFD fed offspring. These results indicate that exercise training plays a beneficial role in preventing MGHT-induced HTRS and that this effect is associated with reduced brain reactivity to pressor stimuli and centrally driven sympathetic activity.

Abstract P172: Impairment Of Estrogen Protective Effect Contributes To Maternal Gestational Hypertension-induced Sensitization Of Hypertensive Response To Post-weaning High Fat Diet In Female Adult Offspring

Obesity/high fat diet (HFD) is a risk factor for cardiovascular diseases including hypertension. Recent evidence indicates that maternal gestational hypertension (MGHT) induces hypertensive response sensitization (HTRS) elicited by post-weaning HFD in both male and female offspring. However, the increase in blood pressure (BP) in female offspring is less than that in male offspring. In this study, we investigated if estrogen plays a protective role in MGHT-induced HTRS to post-weaning HFD in female offspring, and if estrogen effects are associated with regulation of brain reactivity to pressor agents and altered autonomic function. In post-weaning HFD fed intact female offspring, MGHT induced HFD-elicited HTRS (MAP, offspring of NT dams, 107.9±0.9 to 115.2±0.7 mmHg; offspring of MGHT dams, 107.3±0.8 to 120.7±1.4 mmHg, p&lt;0.05) and enhanced pressor responses to centrally administered angiotensin (ANG) II (Δ13.7±1.1 mmHg, p&lt;0.05 vs NFD offspring) and tumor necrosis factor α (TNF-α) (Δ13.1±0.7 mmHg, p&lt;0.05 vs NFD offspring). Ovariectomy (OVX) significantly enhanced the HFD-induced increase in BP (115.2±0.7 to 127.1±2.2 mmHg, p&lt;0.05) and the pressor response to central ANG II (Δ11.2±0.9 to Δ18.7±2.3 mmHg, p&lt;0.05) or TNF-α (Δ10.0±1.0 to Δ16.5±1.6 mmHg, p&lt;0.05) in HFD offspring of normotensive (NT) dams. However, MGHT-induced HTRS (MAP, 122.5±1.9 mmHg) and pressor responses to ANG II (Δ16.3±1.0 mmHg) or TNF-α (Δ14.9±1.0 mmHg) in HFD-fed intact offspring of MGHT dams were not potentiated further after OVX when compared to HFD-fed OVX offspring of NT dams. The resting BP and elicited pressor responses remained higher than that of NFD fed offspring of both NT and MGHT dams. Moreover, OVX induced an increase in central nervous system sympathetic drive, and HFD feeding potentiated this effect. The results indicate that estrogen normally plays a protective role in antagonizing HFD prohypertensive effects in offspring of NT dams. MGHT compromises this normal protective action of estrogen to induce HTRS elicited by HFD, which is through augmenting brain reactivity and centrally driven sympathetic activity.

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson’s Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life.

MO099REPROGRAMMING HYPERTENSION PROGRAMMED BY HIGH-FAT DIET: THE ROLE OF GARLIC OIL

Abstract Background and Aims Perinatal high-fat (HF) diet programs high blood pressure (BP) in adult offspring. Hydrogen sulfide (H2S) has shown benefits in hypertension by restoration of nitric oxide (NO) bioavailability and alterations of gut microbiota. Garlic, a naturally dietary source of H2S donors, supplementation has shown benefits in hypertension. We aimed to examine whether maternal garlic oil supplementation can prevent hypertension programmed by maternal and post-weaning high-fat diet in adult offspring and whether its protective effects are related to mediation of H2S-genetaing system, alterations of gut microbiota composition, and microbiota metabolite short chain fatty acids (SCFAs). Method Pregnant rats received either a normal diet (ND) or HF diet (D12331, Research Diets, Inc.) Garlic oil (GO) or vesicle was administered daily by oral gavage at 100 mg/kg/day during pregnancy and lactation. Male offspring were weaned at 3 weeks of age, and onto either ND or HF diet to 16 weeks of age. Male offspring were assigned to four groups (n=8/group): ND, HF, ND+GO, and HF+GO. Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. All offspring were killed at 16 weeks of age. NO-related parameters were analyzed by HPLC. Plasma levels of SCFA were determined using GC-MS method. Fecal microbial community was analyzed using a combination of 16S rRNA gene and fecal metagenome sequence analysis. Results Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. Garlic oil supplementation caused a significant increase in plasma levels of acetate, propionate, and butyrate. NO bioavailability was augmented by garlic oil supplementation, represented by decreases of plasma levels of asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, and increased plasma L-arginine-to-ADMA ratio (AAR). HF intake associated with decreased α-diversity was quantified by Shannon diversity index. The Analysis of similarities (ANOSIM) demonstrated the difference in the gut microbiota among the four groups existed (All p &amp;lt; 0.05), indicating that four groups had distinct enterotypes. Additionally, garlic oil supplementation increased abundance of genus Lactobacillus, but decreased genera Turicibacter and Staphylococcus. Moreover, the linear discriminant analysis effect size (LEfSe) algorithm analysis identified several microbial markers including genera Lactobacillus, Staphylococcus, and Turicibacter. Conclusion The beneficial effects of garlic oil were associated with increased renal mRNA expression and activity of H2S-generating enzymes, increased NO bioavailability, increased plasma SCFA levels, and alterations of gut microbiota composition. Our data revealed associations between H2S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension programmed by HF intake and provided insight to garlic oil as a hypertension reprogramming strategy for further translational research.

Repercussion of Maternal Diabetes and Post-Weaning High-Fat Diet Consumption in Laboratory Animals

Background: Epidemiological and animal studies show diabetes-induced fetal programming can lead to adverse complications in the late-life of offspring. Western society consumes more calorie-rich foods every day. Objective: In order to understand the association between the influence of a hyperglycemic intrauterine environment and the consumption of a high-fat diet after weaning, this study was carried out with laboratory animals to reproduce the conditions of our current society. Methods: Adult Sprague Dawley rats from mothers with mild diabetes were mated with healthy males to obtain offspring. The female pups (2/mother) were fed a standard (OD/SD, n=9 rats) or high-fat (OD/HFD, n=12 rats) diet from weaning up to adulthood. At four months old, the oral glucose tolerance test (OGTT) was carried out before pregnancy and confirmed glucose intolerance status in both groups. Following, the rats were submitted to cesarean section to evaluate maternal reproductive and fetal development outcomes. P<0.05 was considered for statistically significant difference. Results: At the end of pregnancy, the OD/HFD rats presented a higher percentage of embryo losses, lower number of corpora lutea, alive fetuses, and implantation. The placental and fetal weights were reduced, and the newborns were classified as small for gestational age compared to OD/SD, contributing to the lower litter weight. Conclusion: Our findings suggest the consumption of a post-weaning high-fat diet in association to maternal diabetes influence cause a glucose intolerance at the adulthood of the female offspring and exacerbate impaired reproductive repercussions and fetal development to the next generation.

Bidirectional modulation of hippocampal and amygdala synaptic plasticity by post-weaning obesogenic diet intake in male rats: Influence of the duration of diet exposure.

Obesity is a chronic condition associated with adverse memory and emotional outcomes in humans and animal models. We have recently demonstrated that post-weaning (i.e., periadolescent) high-fat diet (HFD)-induced obesity has opposite effect on hippocampal and amygdala-dependent memory in rodents: while HFD consumption impairs spatial and relational memory, it enhances cue-dependent emotional memory. However, it is still not clear whether this bidirectional HFD effect on memory is related to bidirectional alterations of hippocampal and amygdala synaptic plasticity and if it is influenced by the duration of diet intake. In the current study, we compared in male rats the impact of 2-3 and 6-7 months of HFD intake starting at weaning, thus covering adolescence, on in vivo long-term potentiation (LTP) recorded simultaneously in the hippocampal area CA1 and the basolateral amygdala (BLA). As expected, 6-7 months of HFD intake abolished LTP in the CA1 and enhanced LTP in the BLA. However, 2-3 months of of HFD exposure enhanced LTP in both CA1 and BLA suggesting a transient compensatory mechanism in hippocampus. These results indicate that post-weaning HFD intake progressively leads to bidirectional modulation of hippocampal and amygdala synaptic plasticity, as we previously demonstrated for related memory processes, yet with a different temporal dynamic.