Caloric restriction prevents the development of airway hyperresponsiveness in mice on a high fat diet.
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ABSTRACT:
SUBMITTER: Younas H
PROVIDER: S-EPMC6342916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The experiment was conducted to examine the effect of a high fat diet (HFD) on airway hyperresponsiveness (AHR) in mice. Twenty-three adult male C57BL/6?J mice were fed with HFD or regular chow diet for two weeks. The total respiratory resistance was measured by forced oscillation technique at baseline and after methacholine aerosol challenge at 1, 3, 10 and 30?mg/mL. Bronchoalveolar lavage (BAL) was performed. Lipid levels and lipid peroxidation in lung tissue were measured along with gene expression of multiple cytokines. Lungs were digested, and IL-1? secretion by pulmonary macrophages was determined. HFD feeding resulted in 11% higher body weight compared to chow. HFD did not affect respiratory resistance at baseline, but significantly augmented airway responses to methacholine compared to chow diet (40.5?±?17.7% increase at 30?mg/ml methacholine, p?<?0.05). HFD induced a 3.2?±?0.6 fold increase in IL-1? gene expression (p?<?0.001) and a 38 fold increase in IL-1? secretion in the lungs. There was no change in BAL and no change in any other cytokines, lipid levels or lipid peroxidation. Hence, HFD induced AHR in mice prior to the development of significant obesity which was associated with up-regulation of pulmonary IL-1?.
| S-EPMC5913253 | biostudies-other
Project description:While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.
| S-EPMC3491655 | biostudies-literature
Project description:Diabetes-induced cognitive decline has been recognized in human patients of type 2 diabetes mellitus and mouse model of obesity, but the underlying mechanisms or therapeutic targets are not clearly identified. We investigated the effect of caloric restriction on diabetes-induced memory deficits and searched a molecular mechanism of caloric restriction-mediated neuroprotection. C57BL/6 mice were fed a high-fat diet for 40 weeks and RNA-seq analysis was performed in the hippocampus of high-fat diet-fed mice. To investigate caloric restriction effect on differential expression of genes, mice were fed high-fat diet for 20 weeks and continued on high-fat diet or subjected to caloric restriction (2 g/day) for 12 weeks. High-fat diet-fed mice exhibited insulin resistance, glial activation, blood-brain barrier leakage, and memory deficits, in that we identified neurogranin, a down-regulated gene in high-fat diet-fed mice using RNA-seq analysis; neurogranin regulates Ca(2+)/calmodulin-dependent synaptic function. Caloric restriction increased insulin sensitivity, reduced high-fat diet-induced blood-brain barrier leakage and glial activation, and improved memory deficit. Furthermore, caloric restriction reversed high-fat diet-induced expression of neurogranin and the activation of Ca(2+)/calmodulin-dependent protein kinase II and calpain as well as the downstream effectors. Our results suggest that neurogranin is an important factor of high-fat diet-induced memory deficits on which caloric restriction has a therapeutic effect by regulating neurogranin-associated calcium signaling.
| S-EPMC4908619 | biostudies-literature
Project description:Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.
| S-EPMC6791664 | biostudies-literature
Project description:AIMS/HYPOTHESIS:Hypomagnesaemia (blood Mg2+ <0.7 mmol/l) is a common phenomenon in individuals with type 2 diabetes. However, it remains unknown how a low blood Mg2+ concentration affects lipid and energy metabolism. Therefore, the importance of Mg2+ in obesity and type 2 diabetes has been largely neglected to date. This study aims to determine the effects of hypomagnesaemia on energy homeostasis and lipid metabolism. METHODS:Mice (n?=?12/group) were fed either a low-fat diet (LFD) or a high-fat diet (HFD) (10% or 60% of total energy) in combination with a normal- or low-Mg2+ content (0.21% or 0.03% wt/wt) for 17 weeks. Metabolic cages were used to investigate food intake, energy expenditure and respiration. Blood and tissues were taken to study metabolic parameters and mRNA expression profiles, respectively. RESULTS:We show that low dietary Mg2+ intake ameliorates HFD-induced obesity in mice (47.00?±?1.53 g vs 38.62?±?1.51 g in mice given a normal Mg2+-HFD and low Mg2+-HFD, respectively, p?<?0.05). Consequently, fasting serum glucose levels decreased and insulin sensitivity improved in low Mg2+-HFD-fed mice. Moreover, HFD-induced liver steatosis was absent in the low Mg2+ group. In hypomagnesaemic HFD-fed mice, mRNA expression of key lipolysis genes was increased in epididymal white adipose tissue (eWAT), corresponding to reduced lipid storage and high blood lipid levels. Low Mg2+-HFD-fed mice had increased brown adipose tissue (BAT) Ucp1 mRNA expression and a higher body temperature. No difference was observed in energy expenditure between the two HFD groups. CONCLUSIONS/INTERPRETATION:Mg2+-deficiency abrogates HFD-induced obesity in mice through enhanced eWAT lipolysis and BAT activity.
| S-EPMC6096631 | biostudies-literature
Project description:BackgroundIn mammals, body mass lost during food restriction is often rapidly regained, and fat is accumulated when ad libitum feeding is resumed. Studies in small cold-acclimated mammals have demonstrated significant mobilization of fat deposits during cold exposure to meet the energy requirements of metabolic thermogenesis. However, no studies to our knowledge have examined the effect of cold exposure on fat accumulation during body mass recovery when refed ad libitum. In this study, striped hamsters restricted to 80% of their regular food intake were then refed ad libitum and exposed to one of three conditions: Intermittent cold temperature (5 °C) for 2 h per day (ICE-2 h/d), intermittent cold temperature (5 °C) for 12 h per day (ICE-12 h/d), or persistent cold exposure (PCE) for four weeks. We measured energy intake, fat deposit mass, serum thyroid hormone levels, and uncoupling protein 1 expression in brown adipose tissue.ResultsThere was no significant effect of intermittent or persistent cold exposure on body mass regain, whereas energy intake increased significantly and total fat deposit decreased in the ICE-12 h/d and PCE groups compared to the ICE-2 h/d group and control group maintained at 23 °C (CON). In the ICE-12 h/d and PCE groups, hamsters had 39.6 and 38.3% higher serum 3,3',5-triiodothyronine levels, respectively, and 81.6 and 71.3% up-regulated expression of uncoupling protein 1, respectively, in brown adipose tissue compared to their counterparts in the CON group. The rate of mitochondrial state III and state IV respiration O2 consumption and the activity of cytochrome c oxidase in BAT and liver were significantly higher in the ICE-12 h/d and PCE groups than in the ICE-2 h/d and CON groups.ConclusionsOur findings suggest thyroid hormone-mediated heat production in brown adipose tissue and liver may be involved in preventing fat accumulation during refeeding in animals frequently or persistently exposed to cold conditions.
| S-EPMC10127302 | biostudies-literature
Project description:Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue.
| S-EPMC4651788 | biostudies-other
Project description:We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet.Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight.Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice.
| S-EPMC4681412 | biostudies-literature
Project description:Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.
| S-EPMC5857900 | biostudies-literature
Project description:1. The contribution of reactive nitrogen species to the development of airway hyperresponsiveness in a mouse model of allergic inflammation was investigated by the use of selective inhibitors of nitric oxide and superoxide formation. 2. Sensitized mice, repeatedly challenged with ovalbumin showed a significant (P<0.001, n=9) increase in airway responsiveness measured using whole body plethysmography. This hyperresponsiveness was accompanied by an influx of eosinophils into the airway lumen and increased levels of ovalbumin-specific serum IgE. 3. Treatment of mice with the iNOS inhibitor 1400 W or the NADPH-oxidase inhibitor apocynin did not significantly alter cellular influx into the airway lumen nor serum ovalbumin specific IgE. In contrast, apocynin as well as 1400 W inhibited ovalbumin-induced airway hyperresponsiveness (P<0.001 and P<0.05 respectively, n=9). Furthermore, the airways of allergen challenged animals showed clear 3-nitrotyrosine staining, which was mainly located in eosinophils. Remarkably, treatment with apocynin or 1400 W did not alter 3-nitrotyrosine staining. 4. These data suggest that the development of airway hyperresponsiveness during the airway inflammation upon ovalbumin challenge is dependent on the release of both superoxide and nitric oxide and is therefore likely to be dependent on reactive nitrogen species. This mechanism, however, is not reflected by 3-nitrotyrosine formation in the airways.
| S-EPMC1572946 | biostudies-other