scholarly journals A high-fat diet induces lower expression of retinoid receptors and their target genes GAP-43/neuromodulin and RC3/neurogranin in the rat brain

2010 ◽  
Vol 103 (12) ◽  
pp. 1720-1729 ◽  
Author(s):  
Benjamin Buaud ◽  
Laure Esterle ◽  
Carole Vaysse ◽  
Serge Alfos ◽  
Nicole Combe ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Retinoic Acid ◽  
Fatty Acid ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Target Genes ◽  
Rt Pcr ◽  
High Fat ◽  
Pufa Content ◽  
Protein Levels

Numerous studies have reported an association between cognitive impairment in old age and nutritional factors, including dietary fat. Retinoic acid (RA) plays a central role in the maintenance of cognitive processes via its nuclear receptors (NR), retinoic acid receptor (RAR) and retinoid X receptor (RXR), and the control of target genes, e.g. the synaptic plasticity markers GAP-43/neuromodulin and RC3/neurogranin. Given the relationship between RA and the fatty acid signalling pathways mediated by their respective NR (RAR/RXR and PPAR), we investigated the effect of a high-fat diet (HFD) on (1) PUFA status in the plasma and brain, and (2) the expression of RA and fatty acid NR (RARβ, RXRβγ and PPARδ), and synaptic plasticity genes (GAP-43 and RC3), in young male Wistar rats. In the striatum of rats given a HFD for 8 weeks, real-time PCR (RT-PCR) revealed a decrease in mRNA levels of RARβ ( − 14 %) and PPARδ ( − 13 %) along with an increase in RXRβγ (+52 %). Concomitantly, RT-PCR and Western blot analysis revealed (1) a clear reduction in striatal mRNA and protein levels of RC3 ( − 24 and − 26 %, respectively) and GAP-43 ( − 10 and − 42 %, respectively), which was confirmed by in situ hybridisation, and (2) decreased hippocampal RC3 and GAP-43 protein levels (approximately 25 %). Additionally, HFD rats exhibited a significant decrease in plasma ( − 59 %) and brain ( − 6 %) n-3 PUFA content, mainly due to the loss of DHA. These results suggest that dietary fat induces neurobiological alterations by modulating the brain RA signalling pathway and n-3 PUFA content, which have been previously correlated with cognitive impairment.

scholarly journals Impact of Dietary Fat on the Progression of Liver Fibrosis: Lessons from Animal and Cell Studies

2021 ◽  
Vol 22 (19) ◽  
pp. 10303
Author(s):  
Fangping Jia ◽  
Xiao Hu ◽  
Takefumi Kimura ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Core Gene ◽  
High Fat ◽  
Virus Core ◽  
Liver Fibrogenesis ◽  
Isocaloric Diets

Previous studies have revealed that a high-fat diet is one of the key contributors to the progression of liver fibrosis, and increasing studies are devoted to analyzing the different influences of diverse fat sources on the progression of non-alcoholic steatohepatitis. When we treated three types of isocaloric diets that are rich in cholesterol, saturated fatty acid (SFA) and trans fatty acid (TFA) with hepatitis C virus core gene transgenic mice that spontaneously developed hepatic steatosis without apparent fibrosis, TFA and cholesterol-rich diet, but not SFA-rich diet, displayed distinct hepatic fibrosis. This review summarizes the recent advances in animal and cell studies regarding the effects of these three types of fat on liver fibrogenesis.

scholarly journals Sex differences in cardio-metabolic and cognitive parameters in rats with high-fat diet-induced metabolic dysfunction

2020 ◽  
Vol 245 (11) ◽  
pp. 977-982
Author(s):  
You Kyoung Shin ◽  
Yu Shan Hsieh ◽  
A Young Han ◽  
Soonho Kwon ◽  
Geun Hee Seol
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Cognitive Impairment ◽  
Carotid Artery ◽  
Systolic Blood Pressure ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Fat Intake ◽  
Metabolic Dysfunction ◽  
High Fat

Excessive dietary fat intake is related to metabolic dysfunction and enhances susceptibility to hypertension and cognitive impairment. Although there are sex differences in the prevalence and progression of these diseases, few studies have investigated sex differences in cardio-metabolic and cognitive parameters in rats with high-fat diet-induced metabolic dysfunction. To better reflect actual clinical conditions, sex-differences in rats with high-fat diet-induced metabolic dysfunction were evaluated. Male and female Sprague-Dawley rats were fed a high-fat diet to induce metabolic dysfunction and intraperitoneally injected with N-nitro-L-arginine methyl ester and scopolamine to model vulnerability to hypertension and cognitive impairment, respectively, whereas control rats were fed a regular diet and treated with distilled water and 0.9% saline. Male experimental rats showed significantly higher systolic blood pressure than female experimental animals. More importantly, acetylcholine-induced relaxation of carotid arteries was decreased only in the male experimental rats, revealing a significant difference compared with female experimental rats. These findings provide evidence for individualized sex-based management of patients with metabolic dysfunction and susceptibilities to hypertension and cognitive impairment. Impact statement Excessive dietary fat intake plays important roles in the process of metabolic dysfunction and increases susceptibilities to chronic diseases such as hypertension. Few previous studies, however, have accurately reflected real-world medical conditions. In addition, studies performed to date have not examined detailed sex-differences in cardio-metabolic and cognitive parameters, precluding the development of sex-tailored interventions for patients with metabolic dysfunction who are susceptible to hypertension and cognitive impairment. In this study, using rats with HFD-induced metabolic dysfunction that made them susceptible to hypertension and cognitive impairment, we demonstrate that male rats show greater impairment of acetylcholine-induced vasorelaxation of the carotid artery and systolic blood pressure compared to female rats. These findings may provide a basis for the early detection of carotid artery dysfunction and systolic blood pressure increase, especially in males.

scholarly journals Soluble Fiber Inulin Consumption Limits Alterations of the Gut Microbiota and Hepatic Fatty Acid Metabolism Caused by High-Fat Diet

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1037
Author(s):  
Mayssa Albouery ◽  
Alexis Bretin ◽  
Bénédicte Buteau ◽  
Stéphane Grégoire ◽  
Lucy Martine ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Gut Microbiota ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Liver Fat ◽  
Soluble Fiber ◽  
High Fat ◽  
Total N ◽  
Hepatic Fatty Acid ◽  
Two Parameters

Diet shapes the gut microbiota which impacts hepatic lipid metabolism. Modifications in liver fat content are associated with metabolic disorders. We investigated the extent of dietary fat and fiber-induced alterations in the composition of gut microbiota and hepatic fatty acids (FAs). Mice were fed a purified low-fat diet (LFD) or high-fat diet (HFD) containing non-soluble fiber cellulose or soluble fiber inulin. HFD induced hepatic decreases in the amounts of C14:0, C16:1n-7, C18:1n-7 and increases in the amounts of C17:0, C20:0, C16:1n-9, C22:5n-3, C20:2n-6, C20:3n-6, and C22:4n-6. When incorporated in a LFD, inulin poorly affected the profile of FAs. However, when incorporated in a HFD, it (i) specifically led to an increase in the amounts of hepatic C18:0, C22:0, total polyunsaturated FAs (PUFAs), total n-6 PUFAs, C18:3n-3, and C18:2n-6, (ii) exacerbated the HFD-induced increase in the amount of C17:0, and (iii) prevented the HFD-induced increases in C16:1n-9 and C20:3n-6. Importantly, the expression/activity of some elongases and desaturases, as well as the gut microbiota composition, were impacted by the dietary fat and fiber content. To conclude, inulin modulated gut microbiota and hepatic fatty acid composition, and further investigations will determine whether a causal relationship exists between these two parameters.

scholarly journals The effect of dietary fat on lipogenesis in mammary gland and liver from lactating and virgin mice

1969 ◽  
Vol 115 (4) ◽  
pp. 807-815 ◽  
Author(s):  
Stuart Smith ◽  
Harriet T. Gagné ◽  
Dorothy R. Pitelka ◽  
S. Abraham
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Corn Oil ◽  
Acid Synthesis ◽  
High Fat ◽  
C3h Mice ◽  
Parenchymal Cells

1. Virgin and lactating C3H mice maintained on laboratory chow were transferred to a high-fat (15% corn oil) or a fat-free diet 3 days before being killed. 2. The linoleate content of liver, mammary gland and milk was decreased in lactating mice given the fat-free diet but was increased in those fed on the high-fat diet. Changes in linoleate content and mammary gland followed a similar but much less marked trend in virgin animals. 3. Hepatic fatty acid synthesis in lactating and virgin mice fed on the fat-free diet was higher than in corresponding animals fed on either the chow or the high-fat diet. The lipogenic capacity of livers from mice fed on either the chow or the high-fat diet was greater in lactating than in virgin animals. These changes in hepatic lipogenic capacity were accompanied by alterations in the specific activities of certain enzymes involved in fat synthesis. 4. Mammary gland from virgin and lactating animals showed no such adaptation to dietary fat. Results indicate that fatty acid synthesis in neither mammary-gland parenchymal cells nor mammary-gland adipose cells can be influenced by dietary fat in the same way as in the hepatocyte.

Loss of regulation of lipogenesis in the Zucker diabetic rat. II. Changes in stearate and oleate synthesis

2002 ◽  
Vol 282 (3) ◽  
pp. E507-E513 ◽  
Author(s):  
Sara Bassilian ◽  
Syed Ahmed ◽  
Shu K. Lim ◽  
Laszlo G. Boros ◽  
Catherine S. Mao ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Chain Elongation ◽  
High Fat ◽  
Zdf Rat

De novo lipogenesis and dietary fat uptake are two major sources of fatty acid deposits in fat of obese animals. To determine the relative contribution of fatty acids from these two sources in obesity, we have determined the distribution of c16 and c18 fatty acids of triglycerides in plasma, liver, and epididymal fat pad of Zucker diabetic fatty (ZDF) rats and their lean littermates (ZL) under two isocaloric dietary fat conditions. Lipogenesis was also determined using the deuterated water method. Conversion of palmitate to stearate and stearate to oleate was calculated from the deuterium incorporation by use of the tracer dilution principle. In the ZL rat, lipogenesis was suppressed from 70 to 24%, conversion of palmitate to stearate from 86 to 78%, and conversion of stearate to oleate from 56 to 7% in response to an increase in the dietary fat-to-carbohydrate ratio. The results suggest that suppression of fatty acid synthase and stearoyl-CoA desaturase activities is a normal adaptive mechanism to a high-fat diet. In contrast, de novo lipogenesis, chain elongation, and desaturation were not suppressed by dietary fat in the ZDF rat. The lack of ability to adapt to a high-fat diet resulted in a higher plasma triglyceride concentration and excessive fat accumulation from both diet and de novo synthesis in the ZDF rat.

scholarly journals High Fat Diet Rich in Linoleic Acid Oil Increases Linoleate-Rich Cardiolipin Species in C57BL6/J Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1229-1229
Author(s):  
Connor Mahler ◽  
Austin Angelotti ◽  
Rachel Cole ◽  
Deena Snoke ◽  
Genevieve Sparagna ◽  
...  
Keyword(s):  
Body Weight ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Blood Glucose ◽  
Acid Composition ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Diet Group ◽  
High Fat

Abstract Objectives Dietary fat quality alters the fatty acid composition of phospholipids in cell membranes. The fatty acid composition of the inner mitochondrial membrane phospholipid cardiolipin (CL) impacts mitochondria function where linoleic acid (LA) -rich cardiolipin, e.g., tetralinoleoyl-cardiolipin (L4CL). This study compared the effects of a LA-rich diet and a saturated fat (SF)-rich diet on L4CL in the liver of mice. Methods Male C57BL6/J mice (9 weeks, N = 24) randomized by body weight to a high fat diet (24% fat w/w) containing LA-rich safflower oil (SO) or SF-rich oil (LD) for 18 weeks. Food intake and body weight were measured every two days. Fasting blood glucose and body composition (Echo/MRI) were measured in the washout period and again 11 weeks later. Insulin tolerance test (ITT) measured insulin sensitivity on day 85, and mice were euthanized starting after day 100. Liver cardiolipin speciation was measured using HPLC/MS. A two-sample t-test at a 5% significance level was used to determine differences between diet groups. Results Body weight, cumulative food intake, adipose and lean tissues were not significantly different between diet groups at Day 130. Fasting glucose between diets was not significantly different at any timepoints throughout the study. Blood glucose during the ITT was significantly different between LA-rich and SF-rich diets for the last two time points, 90 minute and 120 minute. The SO diet increased hepatic L4CL (% of total CL) compared to the LD diet (P-value: < 0.01). Conclusions Hepatic CL fatty acid composition reflected dietary fat composition. Feeding of a high fat LA-rich diet increased hepatic L4CL species and hastened resolution of glucose levels in response to insulin in the SO diet group (vs. LD diet group). Funding Sources Supported by Human Nutrition - Human Sciences, Carol S. Kennedy endowment, OADRC.

scholarly journals Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice

2022 ◽  
Vol 12 ◽  
Author(s):  
Lin Zhu ◽  
Julia An ◽  
Sivaprakasam Chinnarasu ◽  
Thao Luu ◽  
Yasminye D. Pettway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Adaptation ◽  
Liver Cholesterol ◽  
Wild Type ◽  
High Fat

Mounting evidence has shown that CETP has important physiological roles in adapting to chronic nutrient excess, specifically, to protect against diet-induced insulin resistance. However, the underlying mechanisms for the protective roles of CETP in metabolism are not yet clear. Mice naturally lack CETP expression. We used transgenic mice with a human CETP minigene (huCETP) controlled by its natural flanking region to further understand CETP-related physiology in response to obesity. Female huCETP mice and their wild-type littermates were fed a high-fat diet for 6 months. Blood lipid profile and liver lipid metabolism were studied. Insulin sensitivity was analyzed with euglycemic-hyperinsulinemic clamp studies combined with 3H-glucose tracer techniques. While high-fat diet feeding induced obesity for huCETP mice and their wild-type littermates lacking CETP expression, insulin sensitivity was higher for female huCETP mice than for their wild-type littermates. There was no difference in insulin sensitivity for male huCETP mice vs. littermates. The increased insulin sensitivity in females was largely caused by the better insulin-mediated suppression of hepatic glucose production. In huCETP females, CETP in the circulation decreased HDL-cholesterol content and increased liver cholesterol uptake and liver cholesterol and oxysterol contents, which was associated with the upregulation of LXR target genes in long-chain polyunsaturated fatty acid biosynthesis and PPARα target genes in fatty acid β-oxidation in the liver. The upregulated fatty acid β-oxidation may account for the improved fatty liver and liver insulin action in female huCETP mice. This study provides further evidence that CETP has beneficial physiological roles in the metabolic adaptation to nutrient excess by promoting liver fatty acid oxidation and hepatic insulin sensitivity, particularly for females.

Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin

2001 ◽  
Vol 281 (2) ◽  
pp. E275-E282 ◽  
Author(s):  
Shaoming Song ◽  
Sofianos Andrikopoulos ◽  
Christine Filippis ◽  
Anne W. Thorburn ◽  
David Khan ◽  
...  
Keyword(s):  
Dietary Fat ◽  
High Fat Diet ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Protein Levels ◽  
Fructose 1,6 Bisphosphatase ◽  
Endogenous Glucose ◽  
Fat Feeding

High-fat feeding has been shown to cause hepatic insulin resistance. The aims of this study were to investigate the biochemical steps responsible for enhanced gluconeogenesis as a result of increased dietary fat intake and the site or sites at which the antihyperglycemic agent metformin acts to inhibit this process. Male Hooded Wistar rats were fed either a standard chow diet (5% fat by weight) or a high-fat diet (60% fat by weight) for 14 days with or without metformin. Total endogenous glucose production and gluconeogenesis were determined using [6-3H]glucose and [U-14C]alanine, respectively. Gluconeogenic enzyme activity and, where appropriate, protein and mRNA levels were measured in liver tissues. The high-fat diet increased endogenous glucose production (21.9 ± 4.4 vs. 32.2 ± 4.8 μmol · kg−1 · min−1, P < 0.05) and alanine gluconeogenesis (4.5 ± 0.9 vs. 9.6 ± 1.9 μmol · kg−1 · min−1, P < 0.05). Metformin reduced both endogenous glucose production (32.2 ± 4.8 vs. 16.1 ± 2.1 μmol · kg−1 · min−1, P < 0.05) and alanine gluconeogenesis (9.6 ± 1.9 vs. 4.7 ± 0.8 μmol · kg−1 · min−1, P < 0.05) after high-fat feeding. These changes were reflected in liver fructose-1,6-bisphosphatase protein levels (4.5 ± 0.9 vs. 9.6 ± 1.9 arbitrary units, P < 0.05 chow vs. high-fat feeding; 9.5 ± 1.9 vs. 4.7 ± 0.8 arbitrary units, P < 0.05 high fat fed in the absence vs. presence of metformin) but not in changes to the activity of other gluconeogenic enzymes. There was a significant positive correlation between alanine gluconeogenesis and fructose-1,6-bisphosphatase protein levels ( r = 0.56, P < 0.05). Therefore, excess supply of dietary fat stimulates alanine gluconeogenesis via an increase in fructose-1,6-bisphosphatase protein levels. Metformin predominantly inhibits alanine gluconeogenesis by preventing the fat-induced changes in fructose-1,6-bisphosphatase levels.

scholarly journals Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

2021 ◽  
Author(s):  
Won-Il Choi ◽  
Jae-Hyun Yoon ◽  
Seo-Hyun Choi ◽  
Bu-Nam Jeon ◽  
Hail Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Target Genes ◽  
Proximal Promoter ◽  
High Fat ◽  
Tissue Mass ◽  
Adipose Tissues ◽  
Adipose Tissue Mass ◽  
Age Dependent ◽  
Treatment Of Diabetes

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

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