scholarly journals Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring

Reproduction ◽  
2011 ◽  
Vol 141 (1) ◽  
pp. 119-126 ◽  
Author(s):  
M A Hyatt ◽  
D S Gardner ◽  
S Sebert ◽  
V Wilson ◽  
N Davidson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Accumulation ◽  
Glucocorticoid Receptors ◽  
Maternal Nutrition ◽  
Fetal Liver ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Gene Expressions ◽  
Triglyceride Accumulation ◽  
Pregnant Sheep

Maternal nutrition during the period of early organ development can modulate the offspring's ability to metabolise excess fat as young adults when exposed to an obesogenic environment. This study examined the hypothesis that exposing offspring to nutrient restriction coincident with early hepatogenesis would result in endocrine and metabolic adaptations that subsequently lead to increased ectopic lipid accumulation within the liver. Pregnant sheep were fed either 50 or 100% of total metabolisable energy requirements from 30 to 80 days gestation and 100% thereafter. At weaning, offspring were made obese, and at ∼1 year of age livers were sampled. Lipid infiltration and molecular indices of gluconeogenesis, lipid metabolism and mitochondrial function were measured. Although hepatic triglyceride accumulation was not affected by obesityper se, it was nearly doubled in obese offspring born to nutrient-restricted mothers. This adaptation was accompanied by elevated gene expression for peroxisome proliferator-activated receptor γ (PPARG) and its co-activator PGC1α, which may be indicative of changes in the rate of hepatic fatty acid oxidation. In contrast, maternal diet had no influence on the stimulatory effect of obesity on gene expression for a range of proteins involved in glucose metabolism and energy balance including glucokinase, glucocorticoid receptors and uncoupling protein 2. Similarly, although gene expressions for the insulin and IGF1 receptors were suppressed by obesity they were not influenced by the prenatal nutritional environment. In conclusion, excess hepatic lipid accumulation with juvenile obesity is promoted by suboptimal nutrition coincident with early development of the fetal liver.

scholarly journals Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes

2019 ◽  
Vol 20 (5) ◽  
pp. 1216 ◽  
Author(s):  
Seok Seo ◽  
Sang-Mi Jo ◽  
Jiyoung Kim ◽  
Myoungsook Lee ◽  
Yunkyoung Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Triglyceride Accumulation ◽  
Mitochondrial Fatty Acid ◽  
Adipocyte Cell ◽  
Underlying Mechanisms

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [3H]-oleic acid (OA) to [3H]-H2O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation.

Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring

2013 ◽  
Vol 25 (5) ◽  
pp. 728 ◽  
Author(s):  
H. P. Fainberg ◽  
D. Sharkey ◽  
S. Sebert ◽  
V. Wilson ◽  
M. Pope ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Accumulation ◽  
Kidney Development ◽  
Maternal Nutrition ◽  
Energy Requirement ◽  
Kidney Cortex ◽  
Fetal Kidney ◽  
The Metabolic Syndrome ◽  
Pregnant Sheep ◽  
Juvenile Obesity

Reduced maternal food intake between early-to-mid gestation results in tissue-specific adaptations in the offspring following juvenile-onset obesity that are indicative of insulin resistance. The aim of the present study was to establish the extent to which renal ectopic lipid accumulation, as opposed to other markers of renal stress, such as iron deposition and apoptosis, is enhanced in obese offspring born to mothers nutrient restricted (NR) throughout early fetal kidney development. Pregnant sheep were fed either 100% (control) or NR (i.e. fed 50% of their total metabolisable energy requirement from 30–80 days gestation and 100% at all other times). At weaning, offspring were made obese and, at approximately 1 year, kidneys were sampled. Triglyceride content, HIF-1α gene expression and the protein abundance of the outer-membrane transporter voltage-dependent anion-selective channel protein (VDAC)-I on the kidney cortex were increased in obese offspring born to NR mothers compared with those born to controls, which exhibited increased iron accumulation within the tubular epithelial cells and increased gene expression of the death receptor Fas. In conclusion, suboptimal maternal nutrition coincident with early fetal kidney development results in enhanced renal lipid deposition following juvenile obesity and could accelerate the onset of the adverse metabolic, rather than cardiovascular, symptoms accompanying the metabolic syndrome.

scholarly journals Ruscogenin Ameliorates Experimental Nonalcoholic Steatohepatitis via Suppressing Lipogenesis and Inflammatory Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hung-Jen Lu ◽  
Thing-Fong Tzeng ◽  
Shorong-Shii Liou ◽  
Chia Ju Chang ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nonalcoholic Steatohepatitis ◽  
Hepg2 Cells ◽  
Inflammatory Responses ◽  
Smooth Muscle Actin ◽  
Liver Steatosis ◽  
Acid Oxidation ◽  
Mrna Levels ◽  
Protective Effects ◽  
Triglyceride Accumulation

The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 μmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 μmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-)κB, andα-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins inβ-oxidation pathway.

Oleoyl-oestrone inhibits lipogenic, but maintains thermogenic, gene expression of brown adipose tissue in overweight rats

2009 ◽  
Vol 29 (4) ◽  
pp. 237-243 ◽  
Author(s):  
María del Mar Romero ◽  
José A. Fernández-López ◽  
Montserrat Esteve ◽  
Marià Alemany
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Critical Factor ◽  
Hormone Sensitive Lipase ◽  
Male Rats ◽  
Acid Oxidation ◽  
Lipase Gene ◽  
Brown Adipose

In the present study we intended to determine how BAT (brown adipose tissue) maintained thermogenesis under treatment with OE (oleoyl-oestrone), a powerful slimming hormone that sheds off body lipid but maintains the metabolic rate. Overweight male rats were subjected to daily gavages of 10 nmol/g of OE or vehicle (control) for 10 days. A PF (pair-fed) vehicle-receiving group was used to discount the effects attributable to energy availability limitation. Interscapular BAT mass, lipid, DNA, mRNA and the RT-PCR (real-time PCR) expression of lipid and energy metabolism genes for enzymes and regulatory proteins were measured. BAT mass and lipid were decreased in OE and PF, with the latter showing a marked reduction in tissue mRNA. Maintenance of perilipin gene expression in PF and OE rats despite the loss of lipid suggests the preservation of the vacuolar interactive surface, a critical factor for thermogenic responsiveness. OE and, to a lesser extent, PF maintained the expression of genes controlling lipolysis and fatty acid oxidation, but markedly decreased the expression of those genes involved in lipogenic and acyl-glycerol synthesis. OE did not affect UCP1 (uncoupling protein 1) (decreased in PF), β3 adrenergic receptors or hormone-sensitive lipase gene mRNAs, which may translate in maintaining a full thermogenic system potential. OE rats were able to maintain a less energetically stressed BAT (probably through glucose utilization) than PF rats. These changes were not paralleled in PF rats, in which lower thermogenesis and glucose preservation resulted in a heavier toll on internal fat stores. Thus the mechanism of action of OE is more complex and tissue-specific than previously assumed.

scholarly journals Gomisin N from Schisandra chinensis Ameliorates Lipid Accumulation and Induces a Brown Fat-Like Phenotype through AMP-Activated Protein Kinase in 3T3-L1 Adipocytes

2020 ◽  
Vol 21 (6) ◽  
pp. 2153
Author(s):  
Kippeum Lee ◽  
Yeon-Joo Lee ◽  
Kui-Jin Kim ◽  
Sungwoo Chei ◽  
Heegu Jin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lipid Accumulation ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Acid Oxidation ◽  
Schisandra Chinensis ◽  
White Adipocytes ◽  
Gomisin N ◽  
Amp Activated Protein Kinase

Obesity results from an imbalance between energy intake and energy expenditure, in which excess fat is stored as triglycerides (TGs) in white adipocytes. Recent studies have explored the anti-obesity effects of certain edible phytochemicals, which suppress TG accumulation and stimulate a brown adipocyte-like phenotype in white adipocytes. Gomisin N (GN) is an important bioactive component of Schisandra chinensis, a woody plant endemic to Asia. GN has antioxidant, anti-inflammatory and hepatoprotective effects in vivo and in vitro. However, the anti-obesity effects of GN in lipid metabolism and adipocyte browning have not yet been investigated. In the present study, we aimed to determine whether GN suppresses lipid accumulation and regulates energy metabolism, potentially via AMP-activated protein kinase (AMPK), in 3T3-L1 adipocytes. Our findings demonstrate that GN inhibited adipogenesis and lipogenesis in adipocyte differentiation. Also, GN not only increased the expression of thermogenic factors, including uncoupling protein 1 (UCP1), but also enhanced fatty acid oxidation (FAO) in 3T3-L1 cells. Therefore, GN may have a therapeutic benefit as a promising natural agent to combat obesity.

scholarly journals Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lingling Han ◽  
Jia Li ◽  
Ying Chen ◽  
Wei Wang ◽  
Dan Zhang ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Acid Oxidation ◽  
Acylated Ghrelin ◽  
High Fat ◽  
Glycerol Phosphate ◽  
Isotope Tracer ◽  
Triglyceride Accumulation

This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA-) induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4), AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and uncoupling protein 3 (UCP3) were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM,P<0.05) and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min,P<0.05). The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (allP<0.05), but those in the 10−9and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (allP<0.05). In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation.

scholarly journals Gemigliptin ameliorates Western-diet-induced metabolic syndrome in mice

2017 ◽  
Vol 95 (2) ◽  
pp. 129-139 ◽  
Author(s):  
Seung Hee Choi ◽  
Jaechan Leem ◽  
Sungmi Park ◽  
Chong-Kee Lee ◽  
Keun-Gyu Park ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
De Novo ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Western Diet ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Model Assessment ◽  
Antihyperglycemic Agents ◽  
Triglyceride Accumulation

Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks. Gemigliptin treatment attenuated WD-induced body mass gain, hypercholesterolemia, adipocyte hypertrophy, and macrophage infiltration into adipose tissue, which were accompanied by an increased expression of uncoupling protein 1 in subcutaneous fat. These events contributed to improved insulin sensitivity, as assessed by the homeostasis model assessment of insulin resistance and intraperitoneal insulin tolerance test. Furthermore, gemigliptin reduced WD-induced hepatic triglyceride accumulation via inhibition of de novo lipogenesis and activation of fatty acid oxidation, which was accompanied by AMP-dependent protein kinase activation. Gemigliptin ameliorated WD-induced hepatic inflammation and fibrosis through suppression of oxidative stress. These results suggest that DPP-4 inhibitors may represent promising therapeutic agents for metabolic syndrome beyond their current role as antihyperglycemic agents.

Fish oil feeding alters liver gene expressions to defend against PPARα activation and ROS production

2002 ◽  
Vol 282 (2) ◽  
pp. G338-G348 ◽  
Author(s):  
Mayumi Takahashi ◽  
Nobuyo Tsuboyama-Kasaoka ◽  
Teruyo Nakatani ◽  
Masami Ishii ◽  
Shuichi Tsutsumi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Fatty Acid ◽  
Fish Oil ◽  
Uncoupling Protein ◽  
Favorable Effect ◽  
Safflower Oil ◽  
Gene Expressions ◽  
Antioxidant Genes ◽  
Fish Oil Diet

Fish oil rich in n-3 polyunsaturated fatty acids has been shown to reduce the risk of cardiovascular diseases partly by reduction of blood triglyceride concentration. This favorable effect mainly results from the combined effects of inhibition of lipogenesis by decrease of SREBP-1 and stimulation of fatty acid oxidation by activation of peroxisome proliferator-activated receptor-α (PPARα) in liver. However, because fish oil is easily peroxidized to form hydroperoxides and increases oxidative stress, some defense mechanism(s) against oxidative stress might occur. To understand these complex effects of fish oil diet, the gene expression profile of mice liver was analyzed using high-density oligonucleotide arrays. High-fat diet (60% of total energy intake) as either safflower oil or fish oil (tuna) was given to mice. After 6 mo of feeding, expression levels of a total of 6,521 genes were analyzed. In fish oil diet compared with safflower oil diet, immune reaction-related genes, antioxidant genes (several glutathione transferases, uncoupling protein 2, and Mn-superoxide dismutase), and lipid catabolism-related genes upregulated, whereas cholesterol and fatty acid synthesis-related genes and 17-alpha hydroxylase/C17–20 lyase and sulfotransferases related to production of endogenous PPARα ligands and reactive oxygen species (ROS) downregulated markedly. Because upregulation of these antioxidant genes and downregulation of sulfotransferases were also observed in mice administered fenofibrate, altered gene expression related to antioxidant system observed in fish oil feeding was mediated directly and indirectly by PPARα activation. However, downregulation of 17-alpha hydroxylase/C17–20 lyase was not due to PPARα activation. These data indicate that fish oil feeding downregulated the endogenous PPARα-activation system and increased antioxidant gene expressions to protect against ROS excess.

scholarly journals Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet

2015 ◽  
Vol 113 (12) ◽  
pp. 1835-1843 ◽  
Author(s):  
Li Xu ◽  
Danping Huang ◽  
Qiaolin Hu ◽  
Jing Wu ◽  
Yizhen Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Basal Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Betaine Supplementation

To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague–Dawley rats weighing 100 (sd 2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (P< 0·05) hepatic TAG accumulation induced by high-fat diet, which was also supported by hepatic histology results. Additionally, hepatic betaine–homocysteine methyltransferase activity as well as its mRNA abundance and lecithin level were found increased (P< 0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P< 0·05) activity of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats. High-fat diet inhibited (P< 0·05) the gene expression of hepatic PPARα and CPT1. However, betaine administration in high-fat diet-fed rats elevated (P< 0·05) the gene expression of PPARα and CPT1. Moreover, concentration, gene and protein expressions of hepatic fibroblast growth factor 21 (FGF21) were increased (P< 0·05) in response to betaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (P< 0·05) as well. The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.

Amelioration of high fructose-induced metabolic derangements by activation of PPARα

2002 ◽  
Vol 282 (5) ◽  
pp. E1180-E1190 ◽  
Author(s):  
Yoshio Nagai ◽  
Yoshihiko Nishio ◽  
Takaaki Nakamura ◽  
Hiroshi Maegawa ◽  
Ryuichi Kikkawa ◽  
...  
Keyword(s):  
Target Gene ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Regulatory Element ◽  
Mitochondrial Gene ◽  
Acid Oxidation ◽  
Gene Expressions ◽  
The Metabolic Syndrome ◽  
Fenofibrate Treatment ◽  
High Fructose

To elucidate molecular mechanisms of high fructose-induced metabolic derangements and the influence of peroxisome proliferator-activated receptor-α (PPARα) activation on them, we examined the expression of sterol regulatory element binding protein-1 (SREBP-1) and PPARα as well as its nuclear activation and target gene expressions in the liver of high fructose-fed rats with or without treatment of fenofibrate. After 8-wk feeding of a diet high in fructose, the mRNA contents of PPARα protein and its activity and gene expressions of fatty acid oxidation enzymes were reduced. In contrast, the gene expressions of SREBP-1 and lipogenic enzymes in the liver were increased by high fructose feeding. Similar high fructose effects were also found in isolated hepatocytes exposed to 20 mM fructose in the media. The treatment of fenofibrate (30 mg · kg−1 · day−1) significantly improved high fructose-induced metabolic derangements such as insulin resistance, hypertension, hyperlipidemia, and fat accumulation in the liver. Consistently, the decreased PPARα protein content, its activity, and its target gene expressions found in high fructose-fed rats were all improved by fenofibrate treatment. Furthermore, we also found that the copy number of mitochondrial DNA, the expressions of mitochondrial transcription factor A, ATPase-6 subunit, and uncoupling protein-3 were increased by fenofibrate treatment. These findings suggest that the metabolic syndrome in high fructose-fed rats is reversed by fenofibrate treatment, which is associated with the induction of enzyme expression related to β-oxidation and the enhancement of mitochondrial gene expression.

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