Ameliorative effects of Spirulina supplementation on high fat and micronutrient deficiency associated complications in wistar rats

Dietary diacylglycerol extenuates arterial thrombosis in apoE and LDLR deficient mice

Adipocyte death has been reported in both obese humans and rodents. However, its role in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity has not been studied. We now show using real-time reverse transcription-PCR arrays that adipose tissue of obese mice display a pro-apoptotic phenotype. Moreover, caspase activation and adipocyte apoptosis were markedly increased in adipose tissue from both mice with diet-induced obesity and obese humans. These changes were associated with activation of both the extrinsic, death receptor-mediated, and intrinsic, mitochondrial-mediated pathways of apoptosis. Genetic inactivation of Bid, a key pro-apoptotic molecule that serves as a link between these two cell death pathways, significantly reduced caspase activation, adipocyte apoptosis, prevented adipose tissue macrophage infiltration, and protected against the development of systemic insulin resistance and hepatic steatosis independent of body weight. These data strongly suggest that adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis associated with obesity in both mice and humans. Inhibition of adipocyte apoptosis may be a new therapeutic strategy for the treatment of obesity-associated metabolic complications.

One of the major topics in modern societies is the study of relationships between diet, stress and incidence of metabolic disorders. This study aimed to investigate possible impairment in glucose-stimulated insulin secretion induced by a high-fat (cow intra-abdominal fat) diet in response to acute stress. Male Wistar rats were divided into high-fat and normal diet groups and each group was further divided into stress and control subgroups. Stress was induced by a communication box. Plasma levels of glucose, insulin and corticosterone were measured in both diet groups. Glucose tolerance, homeostasis model assessment of insulin resistance (HOMA-IR) index, glucose-stimulated insulin secretion from isolated islets, food and energy intake as well as body weight were also evaluated. In the normal diet group, physical stress increased plasma glucose concentrations. In both diet groups, plasma corticosterone levels increased after stress. HOMA-IR index decreased in high-fat fed rats. Food intake decreased while energy intake increased in the high-fat diet rats. Body weight in both diet groups increased in a similar manner. The high-fat diet did not affect insulin secretion; however, stress decreased insulin secretion from isolated islets of both diet groups. Only in the high fat diet group did physical stress increase insulin secretion at 16.7 mM glucose. The cow intra-abdominal fat, did not affect either plasma glucose and insulin concentrations or glucose-induced insulin secretion. Interestingly, it seems that the high-fat diet enabled the islets of the physically stressed rats to secrete more insulin in response to high glucose concentrations.

This study aims to investigate the long-term effects of spirulina supplementation in a high-fat diet (HFD) on rumen morphology, rumen fermentation, and the composition of rumen microbiota in lambs. Spirulina is a blue-green microalgae that has been shown to have high nutritional value for livestock. Fifty-four lambs were randomly divided into three groups: a normal chow diet (NCD) group, a high-fat diet (HFD) group, and a high-fat diet supplemented with 3% spirulina (HFD+S) group. Rumen morphology, rumen fermentation, and rumen microbiota were analyzed at the end of the study. Spirulina supplementation improved the concentration of volatile fatty acids and rumen papilla length. Additionally, there was a tendency for an increase in rumen weight and an upregulation of the genes Claudin-1, Claudin-4, and Occludin in the HFD+S group. Pyrosequencing of the 16S ribosomal RNA gene also showed that spirulina supplementation significantly changed the rumen microbiota composition in the HFD group, with a decrease in richness and diversity. Specifically, the relative abundance of Prevotella 9 and Megasphaera was significantly increased in the HFD group compared to the NCD group, while spirulina supplementation reversed these changes. This study suggests that 3% spirulina supplementation can improve rumen development and fermentation, and effectively relieve rumen microbe disorders in lambs caused by a high-fat diet. However, further research is needed to confirm the findings and to examine the long-term effects of spirulina supplementation in different types of livestock and under different dietary conditions.

BackgroundObesity and other metabolic diseases have become epidemic which greatly affect human health. Diets with healthy nutrition are efficient means to prevent this epidemic occurrence. Novel food resources and process technology were needed for these purpose. In this study, Antarctic krill oil (KO) extracted from a dry krill by a procedure of hot pump dehydration in combined with freezing-drying was used to investigate health effect in animals including the growth, lipid and glucose metabolism.MethodsC57BL/6J mice were fed with a lard based high fat (HF) diet and substituted with KO for a period of 12 weeks in comparison with low fat normal control (NC) diet. Mice body weight and food consumption were recorded. Serum lipid metabolism - of C57BL/6J mice serum was measured. A glucose tolerance tests (GTTs) and pathology analysis of mice were performed at the end of the experiment.ResultsThe KO fed mice had less body weight gain, less fat accumulation in tissue such as adipose and liver. Dyslipidemia induced by high fat diet was partially improved by KO feeding with significant reduction of serum low density lipoprotein-cholesterol (LDL-C) content. Furthermore, KO feeding also improved glucose metabolism in C57BL/6J mice including a glucose tolerance of about 22% vs. 32% of AUC (area under the curve) for KO vs HF diet and the fast blood glucose level of 8.5 mmol/L, 9.8 mmol/L and 9.3 mmol/L for NC, HF and KO diet groups, respectively. In addition, KO feeding also reduced oxidative damage in liver with a decrease of malondialdehyde (MDA) content and increase of superoxide dismutase (SOD) content.ConclusionThis study provided evidence of the beneficial effects of KO on animal health from the processed technology, particularly on lipid and glucose metabolism. This study confirmed that as the Antarctic krill was extracted with a procedure of efficient energy, it might make it possible for Krill oil to be available for food industry.

Excess cholesterol and fat in the diet: A dangerous liaison for energy expenditure and the liver

Long-term dietary fatty acid intake alters the development of left ventricular hypertrophy, but the linking signaling pathways are unclear. We studied the role and underlying signaling mechanisms of dietary fat intake in the early phase of the hypertrophic process. Rats assigned for 4 weeks of high-oil, high-fat, or standard diet were subjected to angiotensin II (Ang II; 33 microg/kg/h, subcutaneous) or vehicle infusion for 24 h. The Ang II-induced increase in left ventricular mRNA levels of hypertrophy-associated genes was higher in rats fed the high-oil diet compared with the standard diet. Western blotting revealed that, in parallel with changes in gene expression, the high-oil diet increased c-Jun N-terminal kinase phosphorylation (P < 0.001). Ang II increased p38 mitogen-activated protein kinase (MAPK) phosphorylation in rats fed the high-fat diet (3-fold; P < 0.01). The increase in transcription factor activator protein-1 (AP-1) DNA binding activity in response to Ang II was higher in rats fed the high-oil diet compared with those fed the standard diet (P < 0.001). Ang II downregulated inducible nitric oxide synthase mRNA levels in fatty acid-supplemented groups compared with the standard diet group. These results show that dietary fat type modulates the early activation of hypertrophic genes in pressure-overloaded myocardium involving the distinct activation of AP-1 and MAPK signal transduction pathways.

The link between obesity and breast cancer has received much attention because it is associated with an increased risk of breast cancer, an increased incidence of recurrence, higher death rates, and reduced sensitivity to anti-hormonal therapy in post-menopausal women. In addition, obesity is associated with a chronic, low grade inflammatory status. Surprisingly, obesity can have different effects in pre-menopausal women where patient outcome is actually better in obese than lean women. This study was conducted to create an animal model to examine the effects of high-fat (HF) diet on estrogen-dependent mammary tumors in cycling rats. Sprague-Dawley rats were injected with N-Methyl-N-Nitrosourea (MNU) at 6 weeks of age to induce mammary tumors. The next day they received HF diet (45% kcal from fat) or normal fat (NF) diet (10% fat) (n=6-7) and animals were kept on these diets for an average of 15 weeks. Ninety-six percent of rats developed mammary tumors and all the tumors were ER positive. The tumor volume, tumor weight and tumor growth rate were not different between the HF or NF diet groups. Also, the HF diet did not influence the body weight, liver weight and adipose mass weight. However, the expression of pro-inflammatory cytokines, such as TNFa and IL-1b, was significantly up-regulated in tumors of the HF diet group compared to control. Macrophage infiltration was also increased in the tumors of the HF diet group. There was also a tendency of increased NFkB DNA binding activity in the HF diet group. Moreover, macrophage infiltration was significantly correlated with the amount of proinflammatory cytokine gene expression in the HF but not the NF diet group. In agreement with clinical data, cycling rats on the HF diet responded better to tamoxifen than did rats on the NF diet, with a greater reduction in tumor size over 20 days of treatment. Taken together, these results indicate that a HF diet induces a pro-inflammatory tumor microenvironment without causing obesity in cycling rats and that these tumors may be more responsive to endocrine therapy. Our findings also provide a model for future studies into the mechanism by which high fat diet may affect tumor growth and response to therapy in premenopausal women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4248. doi:1538-7445.AM2012-4248

This study examined the different effects of high-fat and capsicum diets on the digestive organs of guinea pigs. Hartley guinea pigs (n = 24) were divided into the high-fat diet (HFD), capsicum diet (CD), and control (C) groups. Guinea pigs in the C, HFD, and CD groups received maintenance feed, high-fat, and capsicum diets, respectively. After 12 weeks of modelling, serum samples were collected for biochemical analysis. Enzyme-linked immunosorbent assay was used to quantify interleukin-1β, interleukin-6, and tumour necrosis factor-α, while haematoxylin-eosin staining was used to observe morphological changes. Blood lipid levels and inflammatory markers in the serum of guinea pigs in HFD and CD groups were significantly elevated than those in the serum of guinea pigs in the C group (P < 0.01). Inflammation and blood lipid disorders were more severe among guinea pigs in the HFD group than among those in the CD and C groups (P < 0.001). Pathological examinations revealed that high-fat and capsicum diets induce damage to the liver, stomach, gallbladder, and colon. Specifically, high-fat diets exhibited more significant effects. High-fat or capsicum diet consumption can damage the digestive organs, causing abnormal lipid metabolism; however, high-fat diets exhibit more significant effects on the digestive organs.

Purpose: The objective of this study was to investigate the effects of a high fructose and fat diet on bone growth and maturation in growing female rats. Methods: Three-week-old female SD rats were randomly assigned to four experimental groups; the control group (CON: fed control diet based on AIN-93G, n = 8); the high-fructose diet group (HFrc: fed control diet with 30% fructose, n = 8); the high-fat diet group (Hfat: fed control diet with 45 kcal% fat, n = 8); and the high-fat diet plus high fructose group (HFrc + HFat: fed diets 45 kcal% fat with 30% fructose, n = 8). Each group was assigned their respective diets for the remaining eight weeks. Bone-related parameters (bone mineral density (BMD) and structural parameters, osteocalcin (OC), deoxypyridinoline (DPD)) and morphologic changes of kidney were analyzed at the end of the experiment. Results: Final body weights and weight gain were higher in the HFat and HFrc + HFat groups and showed higher tendency in the HFrc group compared with those of the CON group (p < 0.05); however, no significant difference in caloric intake was observed among the four experimental groups. The serum OC levels of the HFrc and HFrc + HFat groups were lower than those of the CON and HFat groups (p < 0.05). Urinary levels of DPD did not differ among the experimental groups. BV/TV and Tb.N of trabecular bone were higher in the HFrc + HFat group and showed a higher tendency in the HFrc group than those of the CON and HFat groups (p < 0.05). Tb.Pf of trabecular bone were lower in the HFrc + HFat group than those in the CON and HFat groups (p < 0.05). However, no difference in trabecular BMD was observed among the experimental groups. Cortical bone volume was higher in the HFat and HFrc + HFat groups than in the CON and HFrc groups (p < 0.05). No morphology change in kidney was observed among the experimental groups. Conclusion: Our study suggests that 8 weeks of high-fructose and high fat intake could improve the bone quality (Structural parameters) of trabecular and cortical bone of tibia in growing female rats.

Maternal metabolic disorders like obesity and diabetes type II are known to affect reproductive physiology, ultimately leading to poor fertility. The oocyte and embryo are extremely vulnerable during the periconceptional period to metabolic stressors, leading to disappointing fertility results. Most mouse model research regarding obesity and Western type diets has been performed on the inbred C57BL/6 strain. However, inbred strains are often linked with decreased fertility. Relying only on inbred strains might also limit translation to human (outbred) physiology. To further explore this, we compared the inbred C57BL/6N to an outbred Swiss strain. Five-week-old Swiss (N=30) and C57BL/6N (B6) (N=29) mice were fed a control (CTRL) or a high-fat (HF) diet for 13 weeks. Diets differed in percentage of fat (10% v. 60%). Body weight gain, serum profile (nonesterified fatty acids, cholesterol, and triglycerides), and oocyte quality were studied. Mature oocytes were collected after hormonal stimulation (IP injection of 10IU of pregnant mare serum gonadotropin followed by 10IU of hCG 48h later). To study oocyte quality, Bodipy (lipid droplets), JC-1 (mitochondrial membrane potential), and Cell-Rox Deep Red stainings were performed, as well as transmission electron microscopy to examine mitochondrial structures. All data were analysed using the t-test. In comparison with the CTRL group, the HF diet increased body weight by 18.09 and 27.87% in Swiss and B6, respectively. The HF significantly increased blood cholesterol levels (103.5v. 143.1 mg/dL in Swiss mice, 141.8v. 185.4 mg/dL in B6 mice) in both strains, and tended to increase blood nonesterified fatty acids (P=0.053) and triglycerides (P=0.075) only in Swiss but not in B6 mice. Oocytes collected from the HF diet group contained a larger total volume of lipid droplets (P&amp;lt;0.05) in both strains compared with controls. The mitochondrial membrane potential and Cell-Rox Deep Red were significantly increased (P&amp;lt;0.05) in oocytes of Swiss mice, but not B6 mice, fed a HF diet. Transmission electron microscopy images from HF oocytes showed mitochondria with abnormal morphology, low electron density, and rose petal appearance, resulting in significantly increased mitochondrial abnormalities in Swiss mice on the HF diet (P&amp;lt;0.05). In B6 mice, both CTRL and HF oocytes contained high proportions of abnormal mitochondria compared with the CTRL group of the Swiss mice, explaining the lack of HF diet effects in B6 oocyte ultrastructure. We conclude that a HF diet has a significant effect on both metabolic health and oocyte quality. However, the Swiss model seems more sensitive to a Western type diet insult, making it more suitable for research focusing on metabolic health and oocyte quality than the B6 strain. The HF diet-exposed Swiss mice showed differences (compared with CTRL) in their serum profile. Alterations in mitochondrial activity, structures, and oxidative stress were induced by HF diet in the Swiss mice and not the B6, although B6 oocytes also showed higher lipid droplet accumulation. Furthermore, even the B6 mice that were fed a normal control diet showed deviant oocyte quality, clearly shown by morphological signs of lower quality and mitochondrial abnormalities.

The Search for the Perfect Heart-Healthy Diet

Maternal dairy fat diet does not influence neurotrophin levels and cognitive performance in the rat offspring at adult age

The liver X receptors (LXRs) sense oxysterols and regulate genes involved in cholesterol metabolism. Synthetic agonists of LXRs are potent stimulators of fatty acid synthesis, which is mediated largely by sterol regulatory element-binding protein-1c (SREBP-1c). Paradoxically, an improved hepatic lipid profile by LXR was observed in mice fed a Western high fat (HF) diet. To explore the underlying mechanism, we administered mice normal chow or an HF diet and overexpressed LXRalpha in the liver. The HF diet with tail-vein injection of adenovirus of LXRalpha increased the expression of LXR-targeted genes involved in cholesterol reverse transport but not those involved in fatty acid synthesis. A similar effect was also observed with the use of 22R-hydroxycholesterol, an LXR ligand, in cultured hepatocytes. Consequently, SREBP-1c maturation was inhibited by the HF diet, which resulted from the induction of Insig-2a. Importantly, increased cholesterol level suppressed the expression of 2,3-oxidosqualene cyclase (OSC), which led to an increase in endogenous LXR ligand(s). Furthermore, siRNA-mediated knockdown of OSC expression enhanced LXR activity and selectively up-regulated LXR-targeted genes involved in cholesterol reverse transport. Thus, down-regulation of OSC may account for a novel mechanism underlying the LXR-mediated lipid metabolism in the liver of mice fed an HF diet.

METABOLIC AND COGNITIVE EFFECTS OF HIGH FAT DIET IN MALE AND FEMALE MICE