Obesity, not a high fat, high sucrose diet alone, induced glucose intolerance and cardiac dysfunction during pregnancy and postpartum.
Ontology highlight
ABSTRACT:
SUBMITTER: Chung E
PROVIDER: S-EPMC8433413 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The ability of dietary enrichment with monounsaturated fatty acid (MUFA), n-3 or n-6 polyunsaturated fatty acids (PUFAs) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA-enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO).We fed mice a high saturated fat diet (HF) (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signalling and reactivity of isolated pressurized gracilis arteries.After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance was abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance and indices of insulin signalling (phosphorylated Akt) to normal, whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine was reduced in MO-fed mice compared to normal.We conclude that short-term enrichment of an ongoing high fat diet with n-3 PUFA rich MO, but not MUFA rich OO or n-6 PUFA rich SO, reverses glucose tolerance, insulin signalling and vascular dysfunction.
| S-EPMC3674571 | biostudies-literature
Project description:ObjectiveBreakthroughs in HIV treatment, especially combination antiretroviral therapy (ART), have massively reduced AIDS-associated mortality. However, ART administration amplifies the risk of non-AIDS defining illnesses including obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. Initial reports suggest that ART-associated risk of metabolic syndrome correlates with socioeconomic status, a multifaceted finding that encompasses income, race, education, and diet. Therefore, determination of causal relationships is extremely challenging due to the complex interplay between viral infection, ART, and the many environmental factors.MethodsIn the current study, we employed a mouse model to specifically examine interactions between ART and diet that impacts energy balance and glucose metabolism. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages. Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages.ResultsART-treated mice on a HFD displayed increased fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation.ConclusionThe current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways and impairs glucose metabolism, energy balance, and metabolic dysfunction.
| S-EPMC6001921 | biostudies-literature
Project description:The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding the mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for seven days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.
| S-EPMC8217889 | biostudies-literature
Project description:Background Breakthroughs in HIV treatment, especially antiretroviral therapy (ART), have massively reduced mortality. However, ART-treated individuals display elevated rates of obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. These co-morbidities represent a considerable threat to long-term survival and quality of life. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages. Methods and Results Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages. ART-treated mice on a HFD displayed fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation. Conclusions The current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways in eWAT consistent with macrophage infiltration, resulting in impaired glucose metabolism, energy balance, and metabolic dysfunction.
2018-09-14 | GSE110035 | GEO
Project description:A previous study on neuropeptide FF receptor 2 (NPFFR2)-deficient mice has demonstrated that NPFFR2 is involved in the control of energy balance and thermogenesis. Here, we report on the metabolic impact of NPFFR2 deficiency in male and female mice that were fed either a standard diet (STD) or a high-fat diet (HFD) and each experimental group consisted of 10 individuals. Both male and female NPFFR2 knockout (KO) mice exhibited severe glucose intolerance that was exacerbated by a HFD diet. In addition, reduced insulin pathway signaling proteins in NPFFR2 KO mice fed a HFD resulted in the development of hypothalamic insulin resistance. HFD feeding did not cause liver steatosis in NPFFR2 KO mice of either sex, but NPFFR2 KO male mice fed a HFD had lower body weights, white adipose tissues, and liver and lower plasma leptin levels compared to their wild-type (WT) controls. Lower liver weight in NPFFR2 KO male mice compensated for HFD-induced metabolic stress by increased liver PPARα and plasma FGF21 hepatokine, which supported fatty acid β-oxidation in the liver and white adipose tissue. Conversely, NPFFR2 deletion in female mice attenuated the expression of Adra3β and Pparγ, which inhibited lipolysis in adipose tissue.
| S-EPMC10240834 | biostudies-literature
Project description: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.
| S-EPMC10105473 | biostudies-literature
Project description:High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion wound was created, and wound closure was monitored. Neutrophil and platelet recruitment was assessed by immunofluorescence microscopy. Mice fed the high-fat/sucrose diet-only had greater adiposity (p < 0.005) than normal diet-only fed mice; diet reversal markedly reduced adiposity. Following corneal abrasion, wound closure was delayed by ~6 h (p ≤ 0.01) and, at 30 h post-wounding, fewer neutrophils reached the wound center and fewer extravascular platelets were present at the limbus (p < 0.05). Diet restored normal wound closure and neutrophil and platelet influx in the injured cornea. These data suggest compositional changes to the diet may be an effective diet-based therapeutic strategy for maintaining or restoring corneal health.
| S-EPMC9865780 | biostudies-literature
Project description:Obesity is a risk factor for diabetes and cardiovascular diseases, with the incidence of these disorders becoming epidemic. Pathogenic responses to obesity have been ascribed to adipose tissue (AT) dysfunction that promotes bioactive mediator secretion from visceral AT and the initiation of pro-inflammatory events that induce oxidative stress and tissue dysfunction. Current understanding supports that suppressing pro-inflammatory and oxidative events promotes improved metabolic and cardiovascular function. In this regard, electrophilic nitro-fatty acids display pleiotropic anti-inflammatory signalling actions.It was hypothesized that high-fat diet (HFD)-induced inflammatory and metabolic responses, manifested by loss of glucose tolerance and vascular dysfunction, would be attenuated by systemic administration of nitrooctadecenoic acid (OA-NO2). Male C57BL/6j mice subjected to a HFD for 20 weeks displayed increased adiposity, fasting glucose, and insulin levels, which led to glucose intolerance and pulmonary hypertension, characterized by increased right ventricular (RV) end-systolic pressure (RVESP) and pulmonary vascular resistance (PVR). This was associated with increased lung xanthine oxidoreductase (XO) activity, macrophage infiltration, and enhanced expression of pro-inflammatory cytokines. Left ventricular (LV) end-diastolic pressure remained unaltered, indicating that the HFD produces pulmonary vascular remodelling, rather than LV dysfunction and pulmonary venous hypertension. Administration of OA-NO2 for the final 6.5 weeks of HFD improved glucose tolerance and significantly attenuated HFD-induced RVESP, PVR, RV hypertrophy, lung XO activity, oxidative stress, and pro-inflammatory pulmonary cytokine levels.These observations support that the pleiotropic signalling actions of electrophilic fatty acids represent a therapeutic strategy for limiting the complex pathogenic responses instigated by obesity.
| S-EPMC3928004 | biostudies-literature
Project description:Non-resolving inflammation is a central pathologic component of obesity, insulin resistance, type 2 diabetes and associated morbidities. The resultant hyperglycemia is deleterious to the normal function of many organs and its control significantly improves survival and quality of life for patients with diabetes. Macrophages play critical roles in both onset and progression of obesity-associated insulin resistance. Here we show that systemic activation of inflammation resolution prevents from morbid obesity and hyperglycemia under dietary overload conditions. In gain-of-function studies using mice overexpressing the human resolvin E1 receptor (ERV1) in myeloid cells, monocyte phenotypic shifts to increased patrolling-to-inflammatory ratio controlled inflammation, reduced body weight gain and protected from hyperglycemia on high-fat diet. Administration of a natural ERV1 agonist, resolvin E1, recapitulated the pro-resolving actions gained by ERV1 overexpression. This protective metabolic impact is in part explained by systemic activation of resolution programs leading to increased synthesis of specialized pro-resolving mediators.
| S-EPMC5634420 | biostudies-literature
Project description:Obesity-associated metabolic disorders are rising to pandemic proportions; hence, there is an urgent need to identify underlying molecular mechanisms. Glycogen synthase kinase-3 (GSK-3) signaling is highly implicated in metabolic diseases. Furthermore, GSK-3 expression and activity are increased in Type 2 diabetes patients. However, the isoform-specific role of GSK-3 in obesity and glucose intolerance is unclear. Pharmacological GSK-3 inhibitors are not isoform-specific, and tissue-specific genetic models are of limited value to predict the clinical outcome of systemic inhibiion. To overcome these limitations, we created novel mouse models of ROSA26CreERT2-driven, tamoxifen-inducible conditional deletion of GSK-3 that allowed us to delete the gene globally in an isoform-specific and temporal manner. Isoform-specific GSK-3 KOs and littermate controls were subjected to a 16-week high-fat diet (HFD) protocol. On an HFD, GSK-3α KO mice had a significantly lower body weight and modest improvement in glucose tolerance compared to their littermate controls. In contrast, GSK-3β-deletion-mediated improved glucose tolerance was evident much earlier in the timeline and extended up to 12 weeks post-HFD. However, this protective effect weakened after chronic HFD (16 weeks) when GSK-3β KO mice had a significantly higher body weight compared to controls. Importantly, GSK-3β KO mice on a control diet maintained significant improvement in glucose tolerance even after 16 weeks. In summary, our novel mouse models allowed us to delineate the isoform-specific role of GSK-3 in obesity and glucose tolerance. From a translational perspective, our findings underscore the importance of maintaining a healthy weight in patients receiving lithium therapy, which is thought to work by GSK-3 inhibition mechanisms.
| S-EPMC8834358 | biostudies-literature