Normal-fat Diet Group Research Articles

Effect of Supplementation of Chlorogenic Acid to High-Fat Diet on Growth, Lipid Metabolism, Intestinal and Hepatic Histology, and Gut Microbiota of Spotted Sea Bass (Lateolabrax maculatus).

The study investigated the impact of chlorogenic acid (CGA) supplementation in a high-fat diet (HFD) on growth, lipid metabolism, intestinal and hepatic histology, as well as gut microbiota in spotted sea bass. A total of 540 fish were fed six experimental diets, including a normal fat diet (NFD), a high-fat diet (HFD), and HFD supplemented with 100, 200, 300, and 400 mg/kg CGA (named HFD1, HFD2, HFD3, and HFD4, respectively) for 7 weeks. The results showed that HFD feeding increased growth and hepatic lipid deposition compared to that in the NFD group. Inclusion of 300 mg/kg CGA in HFD decreased the HFD-induced hyperlipemia (p < 0.05). Additionally, compared to the HFD group, the HFD4 group showed significant reductions in serum aspartate transaminase (AST) and alanine transaminase (ALT) levels as well as hepatic malondialdehyde (MDA) content, while also improving liver total antioxidant capacity (T-AOC) (p < 0.05). In the CGA-containing groups, hepatocytes were arranged more neatly than those in the HFD group, and there was a reduction in lipid deposition and hemolysis in the liver. Supplementation of CGA had effects on intestinal structure including an increase in mucosal thickness, as well as villus number and width. The diversity of intestinal flora in the CGA-containing groups was higher than those in the HFD group, and supplementation of 200 mg/kg CGA significantly increased the abundance of intestinal bacteria (p < 0.05). HFD4 feeding increased the intestinal Bacteroidetes to Firmicutes ratio and decreased the abundance of Vibrio. The highest value abundance of Actinobacteriota was found in the HFD2 group. Overall, HFD caused negative effects, and supplementation of 200-400 mg/kg CGA to HFD improved fat deposition, lipid metabolic disorders and liver and gut histology, and increased gut bacterial diversity in spotted sea bass.

Conjugated linoleic acid and L-carnitine combination effects on obesity-related miRNAs in diet-induced obese rats

ObjectivesObesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels. Subjects /methodsForty male Wistar rats weighing 150–200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg−1), CLA (500 mg kg−1), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software. ResultsAt the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression. ConclusionCLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment.

Preimplantation or gestation/lactation high-fat diet alters adult offspring metabolism and neurogenesis.

Poor maternal nutrition during pregnancy is known to impair fetal development. Moreover, the preimplantation period is vulnerable to adverse programming of disease. Here, we investigated the effect of a mouse maternal high-fat diet in healthy non-obese dams during preimplantation or throughout pregnancy and lactation on metabolism-related parameters and hippocampal neurogenesis in adult offspring. Female mice were fed from conception either a normal fat diet (normal fat diet group) or high-fat diet throughout gestation and lactation (high-fat diet group), or high-fat diet only during preimplantation (embryonic high-fat diet group, high-fat diet up to E3.5, normal fat diet thereafter). Maternal high-fat diet caused changes in the offspring, including increased systolic blood pressure, diurnal activity, respiratory quotient, and energy expenditure in high-fat diet females, and increased systolic blood pressure and respiratory quotient but decreased energy expenditure in high-fat diet males. High-fat diet males had a higher density of newborn neurons and a lower density of mature neurons in the dentate gyrus, indicating that exposure to a maternal high-fat diet may regulate adult neurogenesis. A maternal high-fat diet also increased the density of astrocytes and microglia in the hippocampus of high-fat diet males and females. Generally, a graded response (normal fat diet < embryonic high-fat < high-fat diet) was observed, with only 3 days of high-fat diet exposure altering offspring energy metabolism and hippocampal cell density. Thus, early maternal exposure to a fatty diet, well before neural differentiation begins and independently of maternal obesity, is sufficient to perturb offspring energy metabolism and brain physiology with lifetime consequences.

4-PBA Attenuates Fat Accumulation in Cultured Spotted Seabass Fed High-Fat-Diet via Regulating Endoplasmic Reticulum Stress.

Excessive fat accumulation is a common phenomenon in cultured fish, which can cause metabolic disease such as fatty liver. However, the relative regulatory approach remains to be explored. Based on this, two feeding trials were conducted. Firstly, fish were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for eight weeks and sampled at the 2nd, 4th, 6th, and 8th week after feeding (Experiment I). In the first four weeks, fish fed an HFD grew faster than those fed an NFD. Conversely, the body weight and weight gain were higher in the NFD group at the 6th and 8th weeks. Under light and transmission electron microscopes, fat accumulation of the liver was accompanied by an obvious endoplasmic reticulum (ER) swell. Accordingly, the expressions of atf-6, ire-1, perk, eif-2α, atf-4, grp78, and chop showed that ER stress was activated at the 6th and 8th weeks. In Experiment II, 50 mg/kg 4-PBA (an ERs inhibitor) was supplemented to an HFD; this was named the 4-PBA group. Then, fish was fed with an NFD, an HFD, and a 4-PBA diet for eight weeks. As the result, the excessive fat deposition caused by an HFD was reversed by 4-PBA. The expression of ER stress-related proteins CHOP and GRP78 was down-regulated by 4-PBA, and the transmission electron microscope images also showed that 4-PBA alleviated ER stress induced by the feeding of an HFD. Furthermore, 4-PBA administration down-regulated SREBP-1C/ACC/FAS, the critical pathways of fat synthesis. In conclusion, the results confirmed that ER stress plays a contributor role in the fat deposition by activating the SREBP-1C/ACC/FAS pathway. 4-PBA as an ER stress inhibitor could reduce fat deposition caused by an HFD via regulating ER stress.

Comparative acetylome analysis reveals the potential mechanism of high fat diet function in allergic disease

Modern technological lifestyles promote allergic diseases, especially food allergies. The underlying molecular mechanisms remain to be uncovered. Protein acetylation is one of the most important post-translational modifications, and it is involved in regulating multiple body metabolic processes. This study aimed to clarify the effects of a high-fat diet (HFD) on allergy risk and the underlying mechanisms. Four-week-old male C57BL/6J mice were randomly divided into two groups and fed a normal fat diet (NFD) or HFD for 24 weeks. Then, serum lipids were measured, and skeletal muscle was collected for acetylome analysis. Compared with the findings in the NFD group, HFD-fed mice were obese and hyperlipidemic. Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups. Among these, eight acetylated proteins were upregulated in the HFD group. In addition, 13 and 11 proteins were acetylated only in the HFD group and NFD group, respectively. These proteins were mainly involved in regulating energy metabolism and mitochondrial function. This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

EVALUATING THE MORPHOLOGICAL CHARACTERISTICS AND VISCERAL FAT OF MALE MICE GENERATED OBESITY MODEL BY A HIGH-FAT DIET

Background: Obesity is a global health issue caused by consuming too much energy compared to the body's needs, which negatively impacts almost every organ of the body. As a result, generating an experimental obesity model is critical for researching new drugs to improve obesity and its consequences. Objectives: Generating obesity model of male mice over a 6-week period of feeding by a high-fat diet. Materials and methods: In this experimental research, 24 male mice (Swiss albino) of 3,5 weeks old were divided into 2 groups, each containing 12 mice: control group fed by a normal-fat diet (NFD) and obesity group fed by a high-fat diet (HFD) in a period of 6 weeks. Evaluation was conducted at the beginning of research, every 7 days and at the end of the study. Results: The mean of body weight, weight gain, body length, body mass index (BMI), chest and waist circumference of HFD group had a statistically significant difference from the end of week 2. The morphological difference was more remarkable at week 3 (p&lt;0.001). After 6 weeks of study, the weight gain rate of HFD group was 131.32% higher than the NFD group. It was also noticeable that the weight of omental fat and renal fat (both sides) in the HFD group was significantly higher than that of the NFD group (p&lt;0,001). Conclusions: Research has successfully generated an obesity model in male mice after a period of 6 weeks by a HFD (640Kcal/100g, 52-53% lipid).

Retinoic acid promotes tissue vitamin A status and modulates adipose tissue metabolism of neonatal rats exposed to maternal high-fat diet-induced obesity.

Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20, n 4 pups per group were euthanised for different measures. It was found that total retinol concentration in neonatal liver and lung was significantly lower in the HFD group than the NFD group, while the concentrations were significantly increased in the HFDRA group. The HFD group exhibited significantly higher body weight (BW) gain, AT mass, serum leptin and adiponectin, and gene expression of these adipokines in white adipose tissue compared with the NFD group; these measures were significantly reduced in the HFDRA group. BAT UCP2 and UCP3 gene expression were significantly higher in pups receiving RA. In conclusion, repeated RA treatment during the suckling period improved the tissue VA status of neonates exposed to maternal obesity. RA also exerted a regulatory effect on neonatal obesity development by reducing BW gain and adiposity and modulating AT metabolism.

The effect of Berberine on obesity through browning of the inguinal white adipose tissue of male rats

Background: Obesity increases the risk of many diseases. White adipose tissue (WAT) browning is being targeted in the treatment of obesity. Berberine (BR) is a plant alkaloid, used mainly in treatment of diarrhea. Studies revealed that BR improves some metabolic disorders in obese but the browning effect of BR on WAT is not fully investigated.Aim of the work: Testing the possible impact of BR on browning of inguinal WAT (iWAT) of adult male albino rats, and to study its possible ameliorating effect on the obesity associated disturbed lipid profile.Materials and methods: Forty-eight adult male albino rats were divided into two main groups; normally fed diet group (NFD) and high fat diet group (HFD). Normal fat diet group was subdivided into three subgroups. Normal fat diet control group (NFDc) received no treatment. Normal fat diet-berberine low dose (NFD+BRL) group received 5mg/kg body weight (b.w) BR, and normal fat diet-berberine high dose (NFD+BRH) group received 10mg/kg b.w berberine. High fat diet group was subdivided into three subgroups: High fat diet control group (HFDc), high fat diet-berberine low dose (HFD+BRL) group and high fat diet-berberine high dose (HFD+BRH) group. Results: Berberine promoted adipocyte browning in the iWAT, where the beige adipocytes were revealed. In addition, browning markers expression in iWAT; UCP1, PGC-1α and CIDEA increased. Also, BR ameliorated the disturbed lipid profile in HFD group.Conclusion: Berberine showed to be a safe browning agent which also improved the dyslipidemia occurred in HFD group. Berberine high dose showed better results than the lower dose. Thus, we believe that BR has excellent potential as an effective safe anti-obesity agent.

Subcutaneous Adipose Tissue Browning, Serum Orexin-A, and Insulin Resistance Following Aerobic Exercise in High-Fat Diet Obesity Male Wistar Rats.

Background:Subcutaneous adipose tissue (SAT) relative to the other adipose tissues may have different roles in health and insulin resistance. The purpose of this study was to investigate the effectiveness of aerobic exercise on SAT thermogenesis indices, serum orexin-A (OXA), and insulin resistance in high-fat diet-induced obesity male Wistar rats.Methods:Thirty-two male Wistar rats with an average weight of 180–200 g were randomly assigned into 4 equal groups: normal fat diet (NFD), high-fat diet obesity (HFDO), normal fat diet after high-fat diet obesity (HFDO-NFD), and aerobic exercise group with normal fat diet after high-fat diet obesity (HFDO-AEX). Fasting levels of serum OXA, insulin, FBS, high-density lipoproteins, low-density lipoproteins, cholesterol and gene expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and UCP1 in SAT were evaluated. Samples were taken in the HFDO group after obesity-induced and in other groups 48 h after 8 weeks of aerobic exercise.Results:The results showed that HFD significantly decreased serum levels of OXA, HDL-c and gene expression of PGC1α and UCP1 in SAT. In addition, it caused a significant increase in Lee index, FBS, insulin resistance, and serum lipid profile in comparison with the NFD group (P ≤ 0.001). Aerobic exercise significantly modified the changes caused by HFD to the normal levels (P ≤ 0.001).Conclusions:These data suggest that aerobic exercise caused an improvement in insulin resistance and blood lipid profiles through an increase in the serum level of OXA and alteration in the SAT phenotype from white to brown or beige.

Responses of functional miRNA-mRNA regulatory modules to a high-fat diet in the liver of hybrid yellow catfish (Pelteobagrus fulvidraco × P. vachelli)

Fatty liver disease is common in cultured yellow catfish as a result of high fat contents in feeds. However, little is known about the mechanism by which the excessive deposition of liver fat causes fatty liver disease. Hybrid yellow catfish (Pelteobagrus fulvidraco♀ × P. vachelli♂) were fed a high-fat diet (HFD) or a normal-fat diet (NFD) for 60 days. Compared with the NFD group, the HFD group showed lower growth performance, higher hepatosomatic and viscerosomatic indexes, increased hepatic triglyceride and cholesterol contents, and more and larger lipid droplets in liver tissue. Whole transcriptome mRNA libraries and microRNA libraries from fish in the NFD and HFD groups were constructed by high-throughput sequencing. Twelve miRNAs were differentially expressed (DE) between the HFD and NFD groups. Seven negatively correlated DE miRNA–DE mRNA pairs were selected, and the expression patterns of both were confirmed using qRT-PCR. Hybrid yellow catfish showed mediated oxidative degradation of liver glucose and fatty acid peroxidation, regulation of antioxidant enzyme activity, and various immune and inflammatory responses to fat deposition and stress. These findings have important biological significance for protecting the liver against stress, as well as economic significance for establishing healthy aquaculture conditions.

A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice

BackgroundDifferential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0), relative to the shorter-chain SFAs have drawn interest for more accurate nutritional guidelines. However, specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by a high C18:0 diet and high palmitic acid (C16:0) diet.MethodsMale C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0/C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0/C16:0 ratio (LSF) for 10 weeks. An oral glucose tolerance test, 72-h energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an autobiochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using gas chromatography-mass spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in the liver. Pathway analysis and gene ontology analysis were applied to describe the roles of differentially expressed mRNAs.ResultsCompared with the NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups and were much higher in the HSF group than those in the LSF group. Both HSF and LSF mice exhibited distinguishable long non-coding RNA (lncRNA), microRNA and mRNA expression profiles when compared with those of NFD mice. Additionally, more differentially expressed lncRNAs and mRNAs were observed in the HSF group than in the LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified as differentially expressed mRNAs between the HSF group and the LSF group.ConclusionThe high fat diet with a high C18:0/C16:0 ratio induced more severe glucose and lipid metabolic disorders and inflammation and affected expression of more lncRNAs and mRNAs than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the differences in biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.

Vitamin A Status in Neonatal and Weanling Rats Reared by Mothers Consuming Normal and High Fat Diets with or Without Vitamin A Supplementation

Abstract Objectives Although the circulating level of vitamin A (VA) is reported to be significantly lower in obese adults, it is unknown if maternal adiposity would influence the VA status of the offspring. The aim of this study was to investigate the status and distribution of VA in the offspring of rats consuming a normal fat diet (NFD) or a high fat diet (HFD), with or without VA supplementation. Methods Sprague-Dawley rats arrived on their second day of gestation and were randomized to either a NFD (25% fat) or a HFD (50% fat) both with an adequate level of VA at 2.6 mg/kg. Upon the delivery of pups, half of rat mothers from the NFD or HFD cohort were switched to a NFD or a HFD both with supplemented VA at 129 mg/kg (NFD + VA and HFD + VA group), respectively. The other half remained on their diets with adequate VA (NFD and HFD group). At postnatal day 14 (P14) and P25, 4 pups/group were euthanized. At P25, the remaining weanling pups (n = 3/group) were fed diets of their respective mothers until being euthanized at P35. Concentrations of total retinol in serum, liver, visceral white AT (WAT), and brown AT (BAT) were measured by UPLC. Results Through the study, pups in non-supplemented groups showed a normal serum retinol concentration but a marginal liver VA status. At all the time points, serum retinol concentration was significantly (P &amp;lt; 0.05) increased in VA-supplemented groups as compared to non-supplemented ones; no significant difference was noted between the NFD and the HFD group. At P14, serum retinol concentration was significantly lower in the HFD + VA group than in the NFD + VA group. In liver, WAT, and BAT, both the concentration and the mass of total retinol was significantly higher in HFD + VA and NFD + VA group than in their respective control at all the time points, with no significant difference noted between the two control groups. At P25, both the concentration and the mass of total retinol in liver and in WAT was significantly higher in HFD + VA than in NFD + VA group. Conclusions Maternal VA supplementation added to both NFD and HFD raised VA status of the offspring. A lower VA concentration in serum but higher concentration in liver and WAT was observed in the HFD + VA group as compared to the NFD + VA group at given time points, indicating that maternal HFD consumption potentially compromised the availability of functional VA in circulation by increasing its deposition in storage organs. Funding Sources NIH.

Differential Effects of Lycopene Supplementation on Adipose Tissue Development and Redox Status in Weanling Offspring of Rats Consuming a High Fat Diet

Abstract Objectives Dietary patterns high in fat contribute to the onset of cardiometabolic disease through accrual of adipose tissue (AT). Nevertheless, carotenoids, such as lycopene, may disrupt these metabolic perturbations. The purpose of this study was to evaluate AT development, systemic and AT redox status, and cardiometabolic biomarkers during weaning and post-weaning periods of offspring from mothers fed high fat diets with and without lycopene supplementation. Methods Sprague-Dawley rats arrived on the 2nd day of gestation and were randomized to 25% normal fat diet (NFD) or 50% high fat diet (HFD). Upon delivery, half of HFD mothers were transitioned to HFD supplemented with 1% lycopene (HFDL group). Remaining mothers continued NFD or HFD without supplementation. Four pups/litter were euthanized at postnatal day 25 (P25). Beginning at P25, weanling pups were fed diets of their respective mothers until euthanization at P35 (three pups/litter). Visceral white AT (WAT) and brown AT (BAT) mass was determined, as well as lipid peroxides and antioxidant capacity (AC) of these tissues and serum. Cardiometabolic biomarkers were assessed at P25. Results At each time point, HFD groups had significantly greater (P &amp;lt; 0.05) WAT accrual compared to NFD group, sufficiently representing diet-induced obesity. Compared to the HFD group, the HFDL group exhibited significantly greater BAT at P25 (P = 0.025) with a significant reduction in WAT mass (P = 0.004). Such patterns continued into P35, albeit non-significant. At both time points, serum lipid peroxides were significantly lower in the HFDL group compared to the HFD (P = 0.005, P = 0.003, respectively). In contrast, AT results were starkly different such that the HFDL group exhibited significantly greater (P &amp;lt; 0.05) lipid peroxides in WAT and BAT at P25 and P35 compared to HFD group. No significant differences in systemic or AT AC were observed between groups. Furthermore, serum adiponectin and leptin did not differ significantly between groups despite the aforementioned modifications in AT development. Conclusions Results from this exploratory analysis suggest that lycopene may induce favorable alterations in AT development, yet it differentially influences redox status in serum and AT. Additional research is warranted to elucidate molecular mechanisms by which lycopene influences AT biology and redox status. Funding Sources NIH.

Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice

The aim of the present study was to compare different diets used to induce obesity in a head-to-head manner with a focus on insulin resistance and vascular dysfunction. Male C57BL/6J mice were put on standard chow diet (SCD), normal-fat diet (NFD), cafeteria diet (CAF) or high-fat diet (HFD) for 12 weeks starting at the age of 6 weeks. Both CAF and HFD led to obesity (weight gain of 179% and 194%, respectively), glucose intolerance and insulin resistance to a comparable extent. In aortas containing perivascular adipose tissue (PVAT), acetylcholine-induced vasodilation was best in the NFD group and worst in the CAF group. Reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 was observed in both CAF and HFD groups. Plasma coagulation activity was highest in the HFD group and lowest in the SCD group. Even the NFD group had significantly higher coagulation activity than the SCD group. In conclusions, CAF and HFD are both reliable mouse diets in inducing visceral obesity, glucose intolerance and insulin resistance. CAF is more effective than HFD in causing PVAT dysfunction and vascular dysfunction, whereas hypercoagulability was mostly evident in the HFD group. Coagulation activity was higher in NFD than NCD group.

Effects of high-fat diet-induced adipokines and cytokines on colorectal cancer development.

Colorectal cancer (CRC) is the third most common tumor worldwide, and recent epidemiological studies have indicated that obesity contributes to the morbidity and mortality of CRC. Furthermore, obesity‐related adipokines have been shown to be closely related to the incidence of CRC, but the underlying mechanisms are unclear. Here, we investigated the effects of high‐fat diet‐induced adipokines and cytokines on the development of CRC in vitro and in vivo. For the in vivo assays, we divided 2‐week‐old C57BL/6J‐ApcMin/J male mice into three groups: normal‐fat diet (ND), high‐fat and high‐sugar feed (HFHS), and high‐fat and low‐sugar feed (HFLS). After 1 week, all mice were injected with 20 mg·kg−1 1,2‐dimethylhydrazine once weekly for 10 consecutive weeks. Body weight, liver weight, epididymal fat weight and blood glucose levels were greatly increased in HFHS and HFLS groups compared with the ND group, and the expression levels of some adipokines and cytokines were obviously higher in HFHS or HFLS mice compared with ND mice. For the in vitro assays, HCT116 CRC cells were treated with sera of ND, HFHS or HFLS groups, or serum‐free media as a negative control. We observed that sera derived from HFHS or HFLS mice that contain excess adipokines and cytokines promoted the proliferation, migration and invasion of HCT116 cells compared with the ND sera‐conditioned medium or serum‐free medium group. Therefore, high‐fat diet‐induced adipokines and cytokines may promote the progression of CRC in vivo and in vitro.

Abstract 450: Adipose Tissue Browning Induced by Natriuretic Peptide Exerts Thermogenic Actions and Improves Insulin Resistance in an in vivo Model of Diet-Induced Obese Mice

Although natriuretic peptides (NPs) classically act on renal and cardiovascular systems, increasing evidence suggest that NPs also largely coordinate inter-organ metabolic cross-talk with adipose tissues. We recently reported that A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature sensitive manner. We herein investigated whether ANP exerts a significant impact on adipose tissues in vivo, using diet-induced obese mice. C57BL/6 mice were exposed to high-fat diet (HFD) or normal-fat diet (NFD) for 13 weeks, and treated with or without ANP infusion for 3 weeks (0.5 ug/kg/min via osmotic-pump). The ANP infusion significantly increased its serum concentration both in NFD and HFD group. Histological analyses revealed that HFD induced increased brown adipose tissue (BAT) cell size with accumulation of lipid droplets (whitening). ANP treatment significantly suppressed this whitening response (re-browning). Similarly, HFD induced enlarged inguinal white adipose tissue (WAT) lipid droplets, which was significantly reduced by ANP. This was associated with a substantial increase in uncoupling protein-1(UCP1) expression in WAT confirmed by immunohistochemical analysis (browning, n=3 each) and UCP1mRNA analysis (NFD+NP 2.7±0.4 fold vs NFD, P&lt;0.01; HFD+NP 6.4±2.2 fold vs HFD, P&lt;0.05, n=5 each). To determine the functional significance of browning effects of ANP, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed and showed that ANP treatment substantially improved insulin resistance in HFD (p&lt;0.05, n=9 each). Moreover, cold tolerance test (at 4°C for 4 hours) demonstrated that the ANP-treated mice were tolerant to cold exposure, which was more salient in HFD with ANP (Decrease in rectal temperature from baseline [°C]: NFD+ANP –2.4±0.6, HFD –2.5±0.4, HFD+ANP –2.1±0.4, versus NFD –9.2±2.2, P&lt;0.01 each, n=9 each). In conclusion, ANP induces WAT browning and preserves BAT function in obese models, leading to in vivo thermogenesis as well as improvement in insulin resistance. These findings reveal the compensatory roles of natriuretic peptides against the core body temperature fall and insulin resistance in a state of heart failure.

Adipose tissue miRNA level variation through conjugated linoleic acid supplementation in diet-induced obese rats.

Conjugated linoleic acid (CLA), which is an octadecadienoic acid isomer, is believed to play different positive physiological roles, such as lowering body fat. Due to some reported side effects of CLA, like lipodystrophy and impaired glucose metabolism, it is important to establish its safety by understanding detailed molecular mechanisms. One of these mechanisms may be the role of this dietary agent in modifying the function and activity of microRNAs (miRNAs). The aim of the study was to investigate how adipocyte miR-27a and miR-143 expression may be influenced by CLA in obese rats. In this study, 24 male Wistar rats were randomly divided into normal-fat diet (NFD) and high-fat diet (HFD) groups. After 8 weeks, the rats were weighed and half of the diet-induced obese rats were randomly selected to receive 500 mg CLA per 1 kg body weight for 4 weeks. At the end of this period, epididymal fat was isolated to investigate the expression level of miRNAs by real-time polymerase chain reaction (RT-PCR). After 12 weeks, the obese rats in the HFD group, compared with rats in the NFD group, demonstrated a significant decrease in the expression of miR-27a (p < 0.05) and a significant increase in the expression of miR-143 (p < 0.05). In the group which had received CLA for a 4-week period, these events were reversed. Moreover, the rats in this group gained less weight than other rats in HFD groups, although the difference was not statistically significant. In conclusion, this study demonstrated that CLA, as an anti-obesity agent, may minimize abnormal changes in miRNA expression in obesity. This suggests a new pathway for weight loss; however, further studies are needed.

Expression of vitamin D hydroxylases and bone quality in obese mice consuming saturated or monounsaturated enriched high-fat diets

Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D–regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.

Immune profiles of T lymphocyte subsets in adipose tissue of obese mouse induced by high-fat diet

In this study, we analyzed high-fat diet (HFD)-induced time-course changes in proportions of T lymphocyte subsets in adipose tissue.Mice were fed with normal-fat diet (NFD) or HFD for 20 weeks. An autoanalyzer was used to assay plasma concentrations of glucose, cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Stromal vascular cells were isolated from epididymal adipose tissues and labeled with antibodies for cluster of differentiation (CD) 3, CD4, CD8, interferon -g, interleukin (IL)-4, and IL-17 for fluorescence-activated cell sorter. We discovered that weight of epididymal fat pads and perirenal fat in HFD group were higher than that in NFD group. Significant changes in glucose, cholesterol, triglyceride, LDL, and HDL content were detected in sera of mice fed with HFD compared with those provided with NFD. Proportions of CD3+, CD4+, and CD8+ T cells increased significantly in adipose tissues of HFD mice compared with those of NFD mice. Proportions of T helper (Th)1 and Th17 sublineages also increased significantly in HFD group. Long-time HFD-induced obesity can increase proportions of CD3+ T, CD4+ T, and CD8+ T cells in epididymal fat pads, disrupt balance of CD4+ T lymphocyte subsets, and induce progressive Th1 and Th17 biases.

Immune profiles of T lymphocyte subsets in adipose tissue of obese mouse induced by high-fat diet

In this study, we analyzed high-fat diet (HFD)-induced time-course changes in proportions of T lymphocyte subsets in adipose tissue.Mice were fed with normal-fat diet (NFD) or HFD for 20 weeks. An autoanalyzer was used to assay plasma concentrations of glucose, cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Stromal vascular cells were isolated from epididymal adipose tissues and labeled with antibodies for cluster of differentiation (CD) 3, CD4, CD8, interferon -g, interleukin (IL)-4, and IL-17 for fluorescence-activated cell sorter. We discovered that weight of epididymal fat pads and perirenal fat in HFD group were higher than that in NFD group. Significant changes in glucose, cholesterol, triglyceride, LDL, and HDL content were detected in sera of mice fed with HFD compared with those provided with NFD. Proportions of CD3+, CD4+, and CD8+ T cells increased significantly in adipose tissues of HFD mice compared with those of NFD mice. Proportions of T helper (Th)1 and Th17 sublineages also increased significantly in HFD group. Long-time HFD-induced obesity can increase proportions of CD3+ T, CD4+ T, and CD8+ T cells in epididymal fat pads, disrupt balance of CD4+ T lymphocyte subsets, and induce progressive Th1 and Th17 biases.