Supplementation Of High-fat Diet Research Articles

Reduction of histamine H1 receptor binding induced by high-fat diet can be prevented by DHA and dietary fiber in specific brain areas of male rats

High-fat (HF) diet and obesity are risk factors for a number of mental health problems including depression, cognitive dysfunction, dementia, and neurodegenerative diseases. Histamine H1 receptors (H1Rs) are involved in many of these conditions. This study examined H1R receptor binding density in the brain of male rats fed a high-saturated fat (HF) diet, as well as the effect of docosahexaenoic acid (DHA), galacto-oligosaccharide (GOS) and resistant starch (RS) supplementation of HF diet. Alterations of H1R expression in the post-mortem rat brain were detected by [(3)H]-pyrilamine binding autoradiography. We found that HF diet significantly decreased H1R binding densities in the substantia nigra (SN), caudate putamen (CPu), hypothalamic arcuate nucleus (Arc), ventral tegmental area (VTA), piriform cortex (Pir) and primary motor cortex (M1), compared with low-fat fed rats, and the suppression of receptor binding density ranged from 31% to 48%. Interestingly, supplementing the HF diet with 0.5% n-3 polyunsaturated docosahexaenoic acid (DHA) prevented reduction of H1R binding densities in the SN and CPu. Addition of galacto-oligosaccharide (GOS) and resistant starch (RS) to the diet blunted HF induced reduction of H1R ligand binding in the SN and Pir, respectively. In conclusion this study showed that HF diet can alter H1R binding densities in various brain regions, and many of these changes can be prevented by adding DHA, GOS or RS to the diet.

Mo1037 Dysregulated Methionine Metabolism and Hyperhomocysteinemia in Diet-Induced Nonalcoholic Fatty Liver Disease

(Purpose) The inflammasomes trigger the biological maturation of proinflammatory cytokines such as interleukin-1 beta or interleukin 18. They induce inflammation as expected, and also, they mediate host defence against microbial pathogens. Three Nod-like receptors (NLR family; NLRP1, NLRP3, NLRC4) are involved in the assembly of multiprotein complex inflammasomes. Recent advances in understanding pathological organ network such as intestine-to-liver revealed that intestinal inflammasomes have important role in the liver inflammation and fibrosis. It has been reported that intesitinal inflammasome activation plays an important role in the progression of NASH (Nature.2012). The intestinal inflammasome activation induces recovery of NASH and the somatic deletion of inflammasome gene results in progression of NASH. Anti-oxidants, such as vitamin E and pioglitazone have favorable effects in NASH. L-Carnitine plays an important role in mitochondrial beta-oxidation and has been reported to be effective in NASH. In this study, we examined the effects of vitamin E and L-carnitine as antioxidant supplementations on liver pathology and regulation of intestinal inflammasome activation in NASHmouse model.. (Methods)We used streptozotocin(STZ)-treated mouse diabetes model with high fat diet supplementation, known as the NASH hepatocarcinogenesis model (STAM mice). Eight-week-old STAM mice were divided into 3 experimental groups and fed for 4 weeks as follows:(1) high fat diet (S group) (2) high fat diet + L-Carnitine (SC group) (3) high fat diet + vitamin E (SE group). After 4 weeks mice were sacrificed. Following data were compared between these three groups; hepatic histological findings, hepatic 8-OHdG concentration, expression of hepatic inflammatory and hepatic lipogenic genes, and intestinal inflammasome related genes by real time PCR. (Results) In histological analysis, SC group and SE group showed low inflammation and fibrosis compared with S group. The concentration of 8-OHdG was reduced in SC and SE group compared with S group. The hepatic gene expression of inflammatory cytokine TNF-α was down-regulated in SC and SE group. The beta oxidation pathway related genes AOX and MCAD, the peroxisomal proliferator-activated receptor PPAR-α and PPAR-γ were up-regulated in SC and SE group. On the other hand, the intestinal inflammasome related genes were up-regulated in SC and SE group compared with S group. (Conclusion) Vitamin E and L-carnitine may prevent progression of non-alcoholic steatohepatitis with up-regulation of intestinal inflammasome activation.

Supplementation of a High-Fat Diet with Chlorogenic Acid Is Associated with Insulin Resistance and Hepatic Lipid Accumulation in Mice

The increasing prevalence of the metabolic syndrome requires a greater need for therapeutic and prevention strategies. Higher coffee consumption is consistently associated with a lower risk of type 2 diabetes in population studies. Dietary polyphenols have been linked to benefits on several features of the metabolic syndrome. Chlorogenic acid (CGA), a major component of coffee, is one of the most consumed polyphenols in the diet. In our study, we conducted a controlled dietary intervention over 12 weeks in male mice. There were three dietary groups: (i) normal diet, (ii) high-fat diet, and (iii) high-fat diet + CGA. We assessed the effect of CGA at a physiologically obtainable dose (1 g/kg of diet) on high-fat-diet-induced obesity, glucose intolerance, insulin resistance, and also fatty acid oxidation and insulin signaling in C57BL/6 male mice. Supplementation of CGA in the high-fat diet did not reduce body weight compared to mice fed the high-fat diet alone (p = 0.32). CGA resulted in increased insulin resistance compared to mice fed a high-fat diet only (p < 0.05). CGA resulted in decreased phosphorylation of AMP-activated protein kinase (AMPK) (p < 0.001) and acetyl carboxylase β (ACCβ), a downstream target of AMPK (p < 0.05), in liver. The liver of mice fed a high-fat diet supplemented with CGA had a higher lipid content (p < 0.05) and more steatosis relative to mice fed a high-fat diet only, indicating impaired fatty acid oxidation. This study suggests that CGA supplementation in a high-fat diet does not protect against features of the metabolic syndrome in diet-induced obese mice.

Implication of fermentable carbohydrates targeting the gut microbiota on conjugated linoleic acid production in high-fat-fed mice

In vitro experiments have shown that isolated human gut bacteria are able to metabolise PUFA into conjugated PUFA like conjugated linoleic acids (CLA). The hypothesis of the present paper was that high-fat (HF) diet feeding and supplementation with fermentable carbohydrates that have prebiotic properties modulate the in vivo production of CLA by the mouse gut microbiota. Mice were treated for 4 weeks as follows: control (CT) groups were fed a standard diet; HF groups were fed a HF diet rich in linoleic acid (18 : 2n-6); the third groups were fed with the HF diet supplemented with either inulin-type fructans (HF-ITF) or arabinoxylans (HF-Ax). HF diet feeding increased rumenic acid (cis-9,trans-11-18 : 2 CLA) content both in the caecal and liver tissues compared with the CT groups. ITF supplementation had no major effect compared with the HF diet whereas Ax supplementation increased further rumenic acid (cis-9,trans-11-18 : 2 CLA) in the caecal tissue. These differences between both prebiotics may be linked to the high fat-binding capacity of Ax that provides more substrates for bacterial metabolism and to differential modulation of the gut microbiota (specific increase in Roseburia spp. in HF-Ax v. HF). In conclusion, these experiments supply the proof of concept that the mouse gut microbiota produces CLA in vivo, with consequences on the level of CLA in the caecal and liver tissues. We postulate that the CLA-producing bacteria could be a mediator to consider in the metabolic effects of both HF diet feeding and prebiotic supplementation.

Anti-Obesity effects of Chang-Chul-Eui-Ee-In-Tang (苍术薏苡仁汤) in female rats with diet-induced obesity

To investigate the effects of Chang-Chul-Eui-Ee-In-Tang ([see text], CCEET), modififi ed CCEET (MCCEET), and Semen Coicis (SC, a major component of CCEET) on energy and glucose homeostasis. The possible mechanism of action of CCEET was also determined. A total of 100 Sprague Dawley female rats were randomly assigned to 5 groups, with 20 in each group. Rats in 4 groups were fed with a high fat diet supplementation (2 g/kg body weight), and water extracts of CCEET, MCCEET, SC, and cellulose (negative control), respectively. The last group was fed with a low-fat diet as a positive control. CCEET and MCCEET decreased body weight and body fat (mesenteric and retroperitoneal fat) more than SC. This decrease was due to decreased energy intake and increased energy expenditure and fat oxidation. The improvement in energy homeostasis was associated with the enhancement of the hypothalamic leptin signalling pathway involving potentiating the phosphorylation of the signal transducer and activator of transcription-3, as well as attenuating the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK). Both CCEET and MCCEET improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test but MCCEET had a better effect than CCEET. Both CCEET and MCCEET safely exerted anti-obesity effects by enhancing energy balance in female rats with diet-induced obesity; MCCEET showed a better effect on glucose homeostasis.

Dietary supplementation with phytosterol and ascorbic acid reduces body mass accumulation and alters food transit time in a diet-induced obesity mouse model

Previous research indicates that animals fed a high fat (HF) diet supplemented with disodium ascorbyl phytostanyl phosphate (DAPP) exhibit reduced mass accumulation when compared to HF control. This compound is a water-soluble phytostanol ester and consists of a hydrophobic plant stanol covalently bonded to ascorbic acid (Vitamin C). To provide insight into the mechanism of this response, we examined the in vivo effects of a high fat diet supplemented with ascorbic acid (AA) in the presence and absence of unesterified phytosterols (PS), and set out to establish whether the supplements have a synergistic effect in a diet-induced obesity mouse model. Our data indicate that HF diet supplementation with a combination of 1% w/w phytosterol and 1% w/w ascorbic acid results in reduced mass accumulation, with mean differences in absolute mass between PSAA and HF control of 10.05%; and differences in mass accumulation of 21.6% (i.e. the PSAA group gained on average 21% less mass each week from weeks 7-12 than the HF control group). In our previous study, the absolute mass difference between the 2% DAPP and HF control was 41%, while the mean difference in mass accumulation between the two groups for weeks 7-12 was 67.9%. Mass loss was not observed in animals supplemented with PS or AA alone. These data suggest that the supplements are synergistic with respect to mass accumulation, and the esterification of the compounds further potentiates the response. Our data also indicate that chronic administration of PS, both in the presence and absence of AA, results in changes to fecal output and food transit time, providing insight into the possibility of long-term changes in intestinal function related to PS supplementation.

Oleuropein attenuates hepatic steatosis induced by high-fat diet in mice

Oleuropein, a secoiridoid derived from olives and olive oil, has been known to possess antimicrobial, antioxidative, and anticancer activities. The purpose of the present study was to determine whether oleuropein has a protective effect against hepatic steatosis induced by a high fat diet (HFD) and to elucidate its underlying molecular mechanisms in mice. Male C57BL/6N mice were fed a normal diet (ND), HFD, or an oleuropein-supplemented diet (OSD) for 10 weeks. The plasma and hepatic lipid levels were determined, and the hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. The supplementation of HFD with oleuropein reversed the HFD-induced increases in liver weight along with plasma and hepatic lipid levels in mice. The expression of Wnt10b inhibitor genes, such as secreted firizzed-related sequence protein 5 and dickkopf homolog 2, was downregulated, whereas the β-catenin protein expression was upregulated in the liver of OSD-fed mice compared to HFD-fed mice. Fibroblast growth factor receptor 1 (FGFR1), phosphoextracellular-signal-regulated kinase 1/2, cyclin D, and E2F transcription factor 1, along with several key transcription factors and their target genes involved in adipogenesis, were downregulated by oleuropein. OSD-fed mice exhibited decreased expression of the toll-like-receptor-(TLR)-mediated signaling molecules (TLR2, TLR4, and myeloid differentiation primary-response gene 88) and proinflammatory cytokines, in their livers, as compared to HFD mice. These results suggest that the protective effects of oleuropein against HFD-induced hepatic steatosis in mice appear to be associated with the Wnt10b- and FGFR1-mediated signaling cascades involved in hepatic lipogenesis, along with the TLR2- and TLR4-mediated signaling implicated in hepatic steatosis.

Immunization of Low-density Lipoprotein Receptor Deficient (LDL-RD) Mice with Heat Shock Protein 65 (HSP-65) Promotes Early Atherosclerosis

Heat shock proteins are a family of approximately 25 highly conserved proteins upregulated in response to various forms of stress. They play an active role in the development autoimmune diseases in animals, and have been incriminated in human autoimmune diseases (i.e. rheumatoid arthritis, multiple sclerosis). It has been previously shown, that an induced immune response against Heat shock protein 65 (HSP-65) results in atherosclerotic lesions in normocholesterolemic rabbits. We have supported these findings showing that C57BL/6 mice immunized with HSP-65 and fed a high-fat diet develop enhanced fatty streaks. To create a model that will eliminate the need for exogenous supplementation of a high-fat diet, we have immunized LDL receptor deficient (LDL–RD) mice with HSP-65 or with heat-killed Mycobacterium tuberculosis (Mt). Seven groups of LDL-RD mice (n=10), were immunized subcutaneously with different concentrations of HSP-65, Mt or bovine serum albumin (BSA). All mice were fed a normal chow-diet for 3 months. The mice immunized with the higher doses of Mt developed significantly larger fatty streaks when compared with their BSA immunized littermates. The size of the lesions in the aortic sinus were: 31,562±5,994μm2in the 10μg Mt and 52,777±5,245μm2in the 100μg Mt vs. 11,500±3,750μm2in the BSA group (P<0.05). In the HSP-65-immunized mice, only the group injected with the highest dose (5μg, twice) developed significantly larger fatty streaks when compared with the BSA-immunized group (28,611±4,716μm2vs. 11,500±3,750μm2respectively, (P<0.05). The HSP-65-but not the Mt- or BSA-immunized mice developed high titers of anti HSP-65 antibodies, beginning 10 days after the immunization, which persisted until they were killed. Immunohistochemical staining showed CD3-positive lymphocytes in the aortic sinus of mice immunized with Mt or HSP-65, but not in the control group. Thus, we established a mouse model of HSP-65 immune mediated atherosclerosis devoid of high fat diet supplementation. This model will enable us to further study the role of the immune system in atherosclerosis, via HSP-65 and raise novel immunomodulatory therapeutic modalities.

Hippocampal serotonin mediates hypoactivity in dietarily obese hamsters: A possible manifestation of aging?

To determine whether endogenous opiates mediate hyperactivity in food restricted hamsters and serotonergic fibers innervating the hippocampus mediate hypoactivity in obese hamsters, food restriction and high-fat diet supplementation were used to produce significant body fat changes (8 vs. 21%). The levels and pattern of spontaneous running were examined after IP saline or naloxone HCl (20 mg/kg) and following the infusion of vehicle and 5,7-dihydroxytryptamine creatine sulfate (4 μg/2 μl) into rostromedial septum of mature female hamsters. Septum-medial preoptic area (POA), hippocampus, hypothalamus, and cortex were dissected from the three groups as well as from two additional groups of hamsters receiving vehicle or neurotoxin. Concentrations of serotonin, norepinephrine, and dopamine were measured in these tissues by HPLC method. Fat-fed hamsters were hypoactive relative to food-restricted hamsters. Naloxone had no significant effect on running behavior. Serotonin neurotoxin increased the running activity of fat-fed hamsters to the level displayed by control hamsters by increasing the number of runs, the total activity level, the speed of running and by decreasing the duration of pauses. Neurotoxin led to selective deletion of serotonin in the hippocampus (77%) and parietal cortex (50%). Serotonergic fibers innervating the hippocampus thus appear to mediate the hypoactivity that is induced by dietary obesity in mature hamsters. Since serotonin mediates some other manifestations of aging, and slow weight increases characterize mid-portion of hamster life span, we hypothesize that serotonergic mediation of hypoactivity is another manifestation of aging.