scholarly journals In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2114 ◽  
Author(s):  
Tanyara B. Payolla ◽  
Caio J. Teixeira ◽  
Fabio T. Sato ◽  
Gilson M. Murata ◽  
Gizela A. Zonta ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Metabolic Disorders ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Utero ◽  
Whole Body ◽  
Hepatic Expression ◽  
Hepatic Lipid Accumulation ◽  
Fructose Intake ◽  
Female Wistar Rats

Distinct environmental insults might interact with fructose consumption and contribute to the development of metabolic disorders. To address whether in utero glucocorticoid exposure and fructose intake modulate metabolic responses, adult female Wistar rats were exposed to dexamethasone (DEX) during pregnancy, and the offspring were administered fructose at a later time. Briefly, dams received DEX during the third period of pregnancy, while control dams remained untreated. Offspring born to control and DEX-treated mothers were defined as CTL-off and DEX-off, respectively, while untreated animals were designated CTL-off-CTL and DEX-off-CTL. CLT-off and DEX-off treated with 10% fructose in the drinking water for 8 weeks are referred to as CTL-off-FRU and DEX-off-FRU. We found that fructose promoted glucose intolerance and whole-body gluconeogenesis in both CTL-off-FRU and DEX-off-FRU animals. On the other hand, hepatic lipid accumulation was significantly stimulated in DEX-off-FRU rats when compared to the CTL-off-FRU group. The DEX-off-FRU group also displayed impaired very-low-density lipoprotein (VLDL) production and reduced hepatic expression of apoB, mttp, and sec22b. DEX-off-FRU has lower hepatic levels of autophagy markers. Taken together, our results support the unprecedented notion that in utero glucocorticoid exposure exacerbates hepatic steatosis caused by fructose consumption later in life.

scholarly journals Liver-specific loss of Perilipin 2 alleviates diet-induced hepatic steatosis, inflammation, and fibrosis

2016 ◽  
Vol 310 (9) ◽  
pp. G726-G738 ◽  
Author(s):  
Charles P. Najt ◽  
Subramanian Senthivinayagam ◽  
Mohammad B. Aljazi ◽  
Kelly A. Fader ◽  
Sandra D. Olenic ◽  
...  
Keyword(s):  
Er Stress ◽  
Hepatic Steatosis ◽  
Stress Proteins ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Tissue Mass ◽  
Hepatic Expression ◽  
Hepatic Lipid Accumulation ◽  
Perilipin 2 ◽  
Progressive Liver Disease

Hepatic inflammation and fibrosis are key elements in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive liver disease initiated by excess hepatic lipid accumulation. Lipid droplet protein Perilipin 2 (Plin2) alleviates dietary-induced hepatic steatosis when globally ablated; however, its role in the progression of NASH remains unknown. To investigate this further, we challenged Plin2 liver-specific knockout mice (designated L-KO) and their respective wild-type (WT) controls with a methionine-choline-deficient (MCD) diet for 15 days to induce a NASH phenotype of increased hepatic triglyceride levels through impaired phosphatidylcholine (PC) synthesis and very-low-density lipoprotein (VLDL) secretion. Results on liver weights, body weights, fat tissue mass, and histology in WT and L-KO mice fed the MCD diet revealed signs of hepatic steatosis, fibrosis, and inflammation; however, these effects were blunted in L-KO mice. In addition, levels of PC and VLDL were unchanged, and hepatic steatosis was reduced in L-KO mice fed the MCD diet, due in part to an increase in remodeling of PE to PC via the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). These mice also exhibited decreased hepatic expression of proinflammatory markers cyclooxygenase 2, IL-6, TNF-α, IL-1β, and reduced expression of endoplasmic reticulum (ER) stress proteins C/EBP homologous protein and cleaved caspase-1. Taken together, these results suggest that Plin2 liver-specific ablation alleviates diet-induced hepatic steatosis and inflammation via a PEMT-mediated mechanism that involves compensatory changes in proteins involved in phospholipid remodeling, inflammation, and ER stress that work to alleviate diet-induced NASH. Overall, these findings support a role for Plin2 as a target for NASH therapy.

scholarly journals The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1281
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Cecilia Nigro ◽  
Paola Mirra ◽  
Claudia Miele ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Plant Extracts ◽  
Elaeis Guineensis ◽  
Low Density Lipoprotein ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Coffea Canephora ◽  
Standard Diet ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

scholarly journals Regulation of very-low-density-lipoprotein lipid secretion in hepatocyte cultures derived from diabetic animals

1989 ◽  
Vol 262 (1) ◽  
pp. 313-319 ◽  
Author(s):  
J M Duerden ◽  
S M Bartlett ◽  
G F Gibbons
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Whole Body ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Short Period ◽  
Streptozotocin Diabetic Rats ◽  
Cholesterol Secretion

Hepatocytes were derived from 2-3-day streptozotocin-diabetic rats and maintained in culture for up to 3 days. Compared with similar cultures from normal animals, these hepatocytes secreted less very-low-density-lipoprotein (VLDL) triacylglycerol, but the decrease in the secretion of VLDL non-esterified and esterified cholesterol was not so pronounced. This resulted in the secretion of relatively cholesterol-rich VLDL particles by the diabetic hepatocytes. Addition of insulin for a relatively short period (24 h) further decreased the low rates of VLDL triacylglycerol secretion from the diabetic hepatocytes. The secretion of VLDL esterified and non-esterified cholesterol also declined. These changes occurred irrespective of whether or not exogenous fatty acids were present in the culture medium. Little or no inhibitory effect of insulin was observed after longer-term (24-48 h) exposure to the hormone. Both dexamethasone and a mixture of lipogenic precursors (lactate plus pyruvate) stimulated VLDL triacylglycerol and cholesterol secretion, but not to the levels observed in hepatocytes from normal animals. The low rate of hepatic VLDL secretion in diabetes contrasts with the increase in whole-body VLDL production rate. This suggests that the intestine is a major source of plasma VLDL in insulin-deficient diabetes.

Clofibrate causes an upregulation of PPAR-α target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

2007 ◽  
Vol 293 (1) ◽  
pp. R70-R77 ◽  
Author(s):  
Sebastian Luci ◽  
Beatrice Giemsa ◽  
Holger Kluge ◽  
Klaus Eder
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Regulatory Element ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-α and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-α target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs ( P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes ( Insig) -1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-α in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-α activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.

scholarly journals Adiponutrin as a Marker of Metabolic Disorders in Patients with Hypertension with Overweight and Obesity

2021 ◽  
Vol 6 (2) ◽  
pp. 77-86
Author(s):  
P. G. Kravchun ◽  
◽  
O. I. Kadykova ◽  
U. S. Herasymchuk
Keyword(s):  
Enzyme Immunoassay ◽  
Carbohydrate Metabolism ◽  
Metabolic Disorders ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Body Mass Index ◽  
Vascular Cognitive Impairment ◽  
Arterial Disease ◽  
Overweight And Obesity ◽  
Control Group

Hypertension is a leading risk factor for coronary heart disease, stroke, peripheral arterial disease, kidney disease, vascular cognitive impairment, and mortality worldwide. Obesity in combination with hypertension continues to attract considerable attention from scientists. Despite the presence of experimental and clinical evidence of mutual burdening of hypertension and obesity, the mechanisms of formation of pathophysiological consequences of such a combination remain insufficiently defined. That is why in recent years an important role is given to the adiponutrin protein. The purpose of the study is to assess the nature of the relationship between adiponutrin levels and lipid and carbohydrate metabolism depending on the duration and degree of hypertension and the degree of obesity in patients with this comorbid pathology. Material and methods. The study included 107 patients with hypertension who were hospitalized in the cardiology department of Municipal noncommercial enterprise "Kharkiv City Clinical Hospital No.27" of Kharkiv municipal council. The age of patients ranged from 32 to 79 years (mean age was 58.6±9.88), who had not previously received regular antihypertensive therapy. The control group consisted of 20 age- and sex-appropriate healthy individuals. The level of adiponutrin was determined in 58 patients with hypertension of the 1st - 3rd degrees, aged from 32 to 79 years (mean age was 57.5±10.11 years), while hypertension of the 1st degree was diagnosed in 12 (20.7%) patients, hypertension of the 2nd degree - in 16 (27.6%), and hypertension of the 3rd degree - in 30 (51.7%) of the examined patients. Blood pressure was measured in patients in a sitting position after 5 minutes of rest, anthropometric measurements were performed, lipid profile and indicators of carbohydrate metabolism were evaluated, adiponutrin levels (pg/mL) were determined by enzyme immunoassay method using The RayBio® Adiponutrin Enzyme Immunoassay (EIA) Kit, (USA). Results and discussion. In all groups of patients with hypertension with overweight and obesity, adiponutrin levels were significantly elevated, and lipid and carbohydrate profiles tended to increase. Significant direct correlations were found between adiponutrine and triglycerides, with very low-density lipoprotein cholesterol of a moderate nature, and draws attention with a very high body mass index. In considering the differences in adiponutrin levels depending on gender, it was found that men have higher adiponutrin levels than women. Conclusion. Thus, we have the opportunity to consider adiponutrin as a marker of metabolic disorders

scholarly journals Ketone Body Rescued Seizure Behavior Of LRP1 Deficiency By Modulating Glutamate Transport

2022 ◽  
Author(s):  
Jin-Ming Zhang ◽  
Ming-Jie Chen ◽  
Jiong-Hui He ◽  
Ya-Ping Li ◽  
Zhi-Cai Li ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Ketone Body ◽  
Low Density Lipoprotein ◽  
Glutamate Transporter ◽  
Density Lipoprotein ◽  
Whole Body ◽  
Control Group ◽  
Seizure Rate ◽  
High Sucrose ◽  
Behavior Test

Abstract LRP1, the low-density lipoprotein receptor 1, would be a novel candidate epilepsy gene according to our bioinformatic results and the animal study. In this study, we explored the role of LRP1 in Epilepsy and whether Beta-hydroxybutyrate, the principal ketone body of the ketogenic diet can treat epilepsy caused by LRP1 deficiency. UAS/GAL4 system was used to establish different genotype models. Flies were given Standard, High-sucrose, and ketone body food randomly. The bang-sensitive test was performed on flies and seizure-like behavior was assessed. Morphologic alteration of LRP1 defect in the brain was detected under GPF expression flies. We established global, astrocytic, and neuronal LRP1 knockdown flies. Whole body and glia LRP1 defect flies had a higher seizure rate compared to the control group in the behavior test. Ketone body decreased the seizure rate in behavior test in all LRP1 defect flies, compared to Standard and High sucrose diet. In morphologic experiments, we found that LRP1 deficiency caused partial loss of the ellipsoidal body and partial destruction of the fan-shaped body. Overexpression of glutamate transporter gene Eaat1 could mimic the ketone body effect on LRP1 deficiency flies. This study demonstrated that LRP1 defect globally or in astrocytes or neurons could induce epilepsy. The ketone body efficaciously rescued epilepsy caused by LRP1 knockdown. The results support screening for LRP1 mutations as discriminating conduct for individuals who require clinical attention and further clarify the mechanism of the ketogenic diet in Epilepsy, which could help Epilepsy patients making a precise treatment case by case.

Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol in healthy young women

2013 ◽  
Vol 304 (2) ◽  
pp. R94-R101 ◽  
Author(s):  
Masanobu Hibi ◽  
Ayumi Masumoto ◽  
Yuri Naito ◽  
Kahori Kiuchi ◽  
Yayoi Yoshimoto ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fat Oxidation ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Night Time ◽  
Snack Consumption

The increase in obesity and lipid disorders in industrialized countries may be due to irregular eating patterns. Few studies have investigated the effects of nighttime snacking on energy metabolism. We examined the effects of nighttime snacking for 13 days on energy metabolism. Eleven healthy women (means ± SD; age: 23 ± 1 yr; body mass index: 20.6 ± 2.6 kg/m2) participated in this randomized crossover trial for a 13-day intervention period. Subjects consumed a specified snack (192.4 ± 18.3 kcal) either during the daytime (10:00) or the night time (23:00) for 13 days. On day 14, energy metabolism was measured in a respiratory chamber without snack consumption. An oral glucose tolerance test was performed on day 15. Relative to daytime snacking, nighttime snacking significantly decreased fat oxidation (daytime snacking: 52.0 ± 13.6 g/day; nighttime snacking: 45.8 ± 14.0 g/day; P = 0.02) and tended to increase the respiratory quotient (daytime snacking: 0.878 ± 0.022; nighttime snacking: 0.888 ± 0.021; P = 0.09). The frequency of snack intake and energy intake, body weight, and energy expenditure were not affected. Total and low-density lipoprotein (LDL) cholesterol significantly increased after nighttime snacking (152 ± 26 mg/dl and 161 ± 29 mg/dl; P = 0.03 and 76 ± 20 mg/dl and 83 ± 24 mg/dl; P = 0.01, respectively), but glucose and insulin levels after the glucose load were not affected. Nighttime snacking increased total and LDL cholesterol and reduced fat oxidation, suggesting that eating at night changes fat metabolism and increases the risk of obesity.

Abstract P080: Fructose Acutely Increases Size of Very Low Density Lipoprotein In Adolescents With Hepatic Steatosis

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mirian Vos ◽  
Ran Jin ◽  
Jean Welsh ◽  
Ngoc-Anh Le
Keyword(s):  
Hepatic Steatosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Complications ◽  
Plasma Lipoproteins ◽  
Healthy Children ◽  
Mri Imaging ◽  
Nonalcoholic Fatty Liver ◽  
Obese Adolescents ◽  
Acute Response

Introduction: Cardiovascular complications are a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). Fructose has been reported to be associated with dyslipidemia and increased cardiovascular risk in adults but its impact on adolescents with NAFLD is not well understood. We previously demonstrated that fructose disproportionately increased postprandial hypertriglyceridemia in pediatric NAFLD as compared to healthy children. However, the mechanism remains unclear. Hypothesis: We hypothesized that fructose would contribute to hypertriglyceridemia in pediatric NAFLD by increasing the size of VLDL particles. Methods: We examined the acute response to a single dose of fructose beverage in 50 Hispanic-American obese adolescents with varying degrees of hepatic steatosis. Those with hepatic fat >5% on MRI imaging were designated as presumed NAFLD. Subjects consumed a 12oz drink containing 33g of fructose and plasma samples were collected at baseline and 30, 60, and 90 minutes afterwards. Plasma lipoproteins were measured using NMR (Liposcience, Raleigh, NC). Results: In response to acute fructose load, subjects without NAFLD increased the total number of TG rich lipoprotein particles (p = 0.047). However, this increase was not observed in subjects with NAFLD; instead, they increased the subpopulation of large VLDL particles (p = 0.008) and the mean size of VLDL particles (p = 0.004) (Figure 1). In line with this finding, TG-to-apoB ratio significantly increased in subjects with NAFLD (2.25 ± 0.26 to 2.37 ± 0.25, p = 0.031) but not in non-NAFLD. Conclusions: These findings demonstrate that adolescents with NAFLD have more atherogenic, large VLDL in response to fructose compared to obese adolescents without NAFLD. Dietary fructose restriction may be a critical component in the treatment of NAFLD associated cardiovascular disease and should be tested further.

scholarly journals ChREBP-Mediated Regulation of Lipid Metabolism: Involvement of the Gut Microbiota, Liver, and Adipose Tissue

2020 ◽  
Vol 11 ◽  
Author(s):  
Katsumi Iizuka ◽  
Ken Takao ◽  
Daisuke Yabe
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Whole Body ◽  
Acetyl Coa ◽  
Alcoholic Fatty Liver

Carbohydrate response element-binding protein (ChREBP) plays an important role in the development of type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, as well as tumorigenesis. ChREBP is highly expressed in lipogenic organs, such as liver, intestine, and adipose tissue, in which it regulates the production of acetyl CoA from glucose by inducing Pklr and Acyl expression. It has recently been demonstrated that ChREBP plays a role in the conversion of gut microbiota-derived acetate to acetyl CoA by activating its target gene, Acss2, in the liver. ChREBP regulates fatty acid synthesis, elongation, and desaturation by inducing Acc1 and Fasn, elongation of long-chain fatty acids family member 6 (encoded by Elovl6), and Scd1 expression, respectively. ChREBP also regulates the formation of very low-density lipoprotein by inducing the expression of Mtp. Furthermore, it plays a crucial role in peripheral lipid metabolism by inducing Fgf21 expression, as well as that of Angptl3 and Angptl8, which are known to reduce peripheral lipoprotein lipase activity. In addition, ChREBP is involved in the production of palmitic-acid-5-hydroxystearic-acid, which increases insulin sensitivity in adipose tissue. Curiously, ChREBP is indirectly involved in fatty acid β-oxidation and subsequent ketogenesis. Thus, ChREBP regulates whole-body lipid metabolism by controlling the transcription of lipogenic enzymes and liver-derived cytokines.

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