scholarly journals A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice

2014 ◽  
Vol 55 (12) ◽  
pp. 2541-2553 ◽  
Author(s):  
Joao A. G. Duarte ◽  
Filipa Carvalho ◽  
Mackenzie Pearson ◽  
Jay D. Horton ◽  
Jeffrey D. Browning ◽  
...  
Keyword(s):  
High Fat Diet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Triglyceride Synthesis

Loss of regulation of lipogenesis in the Zucker diabetic (ZDF) rat

2000 ◽  
Vol 279 (2) ◽  
pp. E425-E432 ◽  
Author(s):  
W.-N. Paul Lee ◽  
Sara Bassilian ◽  
Shu Lim ◽  
Laszlo G. Boros
Keyword(s):  
High Fat Diet ◽  
Leptin Receptor ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Chain Elongation ◽  
Deuterated Water ◽  
High Fat ◽  
Macronutrient Composition ◽  
Zdf Rat

We present here a study on the role of leptin in the regulation of lipogenesis by examining the effect of dietary macronutrient composition on lipogenesis in the leptin receptor-defective Zucker diabetic fatty rat (ZDF) and its lean litter mate (ZL). Animals were pair fed two isocaloric diets differing in their fat-to-carbohydrate ratio providing 10 and 30% energy as fat. Lipogenesis was measured in the rats using deuterated water and isotopomer analysis. From the deuterium incorporation into plasma palmitate, stearate, and oleate, we determined de novo synthesis of palmitate and synthesis of stearate by chain elongation and of oleate by desaturation. Because the macronutrient composition and the caloric density were controlled, changes in de novo lipogenesis under these dietary conditions represent adaptation to changes in the fat-to-carbohydrate ratio of the diet. De novo lipogenesis was normally suppressed in response to the high-fat diet in the ZL rat to maintain a relatively constant amount of lipids transported. The ZDF rat had a higher rate of lipogenesis, which was not suppressed by the high-fat diet. The results suggest an important hormonal role of leptin in the feedback regulation of lipogenesis.

scholarly journals Polyunsaturated Fatty Acids Stimulate De novo Lipogenesis and Improve Glucose Homeostasis during Refeeding with High Fat Diet

2017 ◽  
Vol 8 ◽  
Author(s):  
Raffaella Crescenzo ◽  
Arianna Mazzoli ◽  
Rosa Cancelliere ◽  
Francesca Bianco ◽  
Antonia Giacco ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat

scholarly journals Niacin Ameliorates Hepatic Steatosis by Inhibiting De Novo Lipogenesis Via a GPR109A-Mediated PKC–ERK1/2–AMPK Signaling Pathway in C57BL/6 Mice Fed a High-Fat Diet

2019 ◽  
Vol 150 (4) ◽  
pp. 672-684 ◽  
Author(s):  
Lingyan Ye ◽  
Zheng Cao ◽  
Xiangru Lai ◽  
Ying Shi ◽  
Naiming Zhou
Keyword(s):  
Liver Disease ◽  
Protein Kinase ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Hepatic de novo lipogenesis (DNL) has been suggested to contribute to the pathogenesis of NAFLD. Recent studies have demonstrated that niacin (NA) modulates hepatic DNL through GPR109A. However, the underlying mechanism remains largely unknown. Objectives This study aims to elucidate the potential molecular mechanism by which GPR109A inhibits hepatic DNL. Methods C57BL/6 wild-type (WT) and Gpr109a knockout (KO) mice (male, 5 wk old) were fed a high-fat diet (60% energy from fat) firstly for 6 wk to generate a diet-induced obese model. Subsequently, they were randomly divided into 4 groups for the next 8–9 wk: WT mice with oral water [WT + vehile (VE)], WT mice with oral NA (50 mM, dissolved in water) (WT + NA), KO mice with oral water (KO + VE), and KO mice with oral NA (50 mM) (KO + NA). Mechanisms were examined in HepG2 cells. Body composition, liver histology, biomarkers of hepatic function, lipid accumulation, and lipid synthesis signals in HepG2 cells were measured. Results Upon activation, GPR109A apparently protected against obesity and hepatic steatosis (P < 0.05). The concentrations of hepatic Tnf-α in the WT + NA group were about 50% of those in the WT + VE group (P < 0.05). The activities of serum alanine transaminase and aspartate transaminase were 26.7% and 53.5% lower in the WT + NA group than in the WT + VE group, respectively (P < 0.05). In HepG2 cells, activation of GPR109A resulted in remarkable inhibition of oleic acid–induced lipid accumulation via a protein kinase C–extracellular signal-regulated kinase-1/2–AMP-activated protein kinase signaling pathway. Conclusions NA inhibits hepatic lipogenesis in C57BL/6 mice through a GPR109A-mediated signaling pathway, consistent with the mechanistic studies in HepG2 cells, suggesting its potential for treatment of NAFLD and other fatty liver diseases.

Influence of diet on the modeling of adipose tissue triglycerides during growth

2003 ◽  
Vol 285 (4) ◽  
pp. E917-E925 ◽  
Author(s):  
Daniel Z. Brunengraber ◽  
Brendan J. McCabe ◽  
Takhar Kasumov ◽  
James C. Alexander ◽  
Visvanathan Chandramouli ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
De Novo ◽  
High Carbohydrate Diet ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Carbohydrate Diet ◽  
Triglyceride Synthesis ◽  
High Carbohydrate ◽  
Synthesis And Degradation

We have studied the accretion of lipids in growing mice. We measured the rates of synthesis and degradation of triglycerides in epididymal fat pads of mice maintained for 44 days on a low-fat, high-carbohydrate diet ( I) or a high-fat, lowcarbohydrate diet ( II). 2H2O was added to the drinking water for 14 days. Rates of incorporation/washout of 2H to/from C1 of triglyceride-glycerol showed that triglyceride synthesis was greater than triglyceride degradation (net triglyceride balance was ∼2.5 times greater in II than in I). The data also show that the contribution of de novo lipogenesis to triglyceride-bound palmitate was ∼3 times greater in I than in II. This was consistent with a greater relative intake of carbohydrate in I vs. II. The rates of incorporation and washout of newly synthesized (2H-labeled) palmitate into and from triglycerides were also measured. Those data suggested a remodeling of triglyceride-bound fatty acids. On measuring the profile of triglyceride-bound fatty acids, we observed a decrease in the relative abundance of triglyceride-bound palmitate and stearate and an increase in triglyceride-bound oleate and linoleate. This was observed in I and II. In summary, diet substantially affects the deposition and modeling of triglycerides in adipose tissue during growth. 2H2O can be used to examine the mechanisms responsible for the accumulation of triglycerides, e.g., factors that affect 1) triglyceride synthesis and degradation and 2) the source of fatty acids that are used in esterification.

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 miR-146a regulates insulin sensitivity via NPR3

2020 ◽  
Author(s):  
Julian Roos ◽  
Meike Dahlhaus ◽  
Jan-Bernd Funcke ◽  
Monika Kustermann ◽  
Gudrun Strauss ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
De Novo ◽  
Liver Steatosis ◽  
De Novo Lipogenesis ◽  
Loss Of Function ◽  
High Fat

AbstractThe pathogenesis of obesity-related metabolic diseases has been linked to the inflammation of white adipose tissue (WAT), but the molecular interconnections are still not fully understood. MiR-146a controls inflammatory processes by suppressing pro-inflammatory signaling pathways. The aim of this study was to characterize the role of miR-146a in obesity and insulin resistance. MiR-146a−/− mice were subjected to a high-fat diet followed by metabolic tests and WAT transcriptomics. Gain- and loss-of-function studies were performed using human Simpson–Golabi–Behmel syndrome (SGBS) adipocytes. Compared to controls, miR-146a−/− mice gained significantly more body weight on a high-fat diet with increased fat mass and adipocyte hypertrophy. This was accompanied by exacerbated liver steatosis, insulin resistance, and glucose intolerance. Likewise, adipocytes transfected with an inhibitor of miR-146a displayed a decrease in insulin-stimulated glucose uptake, while transfecting miR-146a mimics caused the opposite effect. Natriuretic peptide receptor 3 (NPR3) was identified as a direct target gene of miR-146a in adipocytes and CRISPR/Cas9-mediated knockout of NPR3 increased insulin-stimulated glucose uptake and enhanced de novo lipogenesis. In summary, miR-146a regulates systemic and adipocyte insulin sensitivity via downregulation of NPR3.

Patchouli Oil Attenuates High Fat Diet-induced Non-alcoholic Hepatic Steatosis

Planta Medica ◽  
2020 ◽  
Vol 86 (04) ◽  
pp. 255-266 ◽  
Author(s):  
Nan Xu ◽  
Xue Wu ◽  
Hui-Juan Luo ◽  
Fang-Fang Xu ◽  
Qiong-Hui Huang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
De Novo ◽  
Regulatory Element ◽  
Chinese Herb ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Very Low Density Lipoproteins ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

scholarly journals Dietary Glycotoxins Impair Hepatic Lipidemic Profile in Diet-Induced Obese Rats Causing Hepatic Oxidative Stress and Insulin Resistance

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
C. Neves ◽  
T. Rodrigues ◽  
J. Sereno ◽  
C. Simões ◽  
J. Castelhano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Fatty Acid ◽  
High Fat Diet ◽  
De Novo ◽  
Liver Lipid ◽  
Lipid Fraction ◽  
De Novo Lipogenesis ◽  
High Fat ◽  
Obese Rats

Nonalcoholic fatty liver disease (NAFLD) is caused by excessive liver lipid accumulation, but insulin resistance is specifically associated with impaired lipid saturation, oxidation, and storage (esterification), besides increased de novo lipogenesis. We hypothesized that dietary glycotoxins could impair hepatic lipid metabolism in obesity contributing to lipotoxicity-driven insulin resistance and thus to the onset of nonalcoholic steatohepatitis (NASH). In diet-induced obese rats with methylglyoxal-induced glycation, magnetic resonance spectroscopy, mass spectrometry, and gas chromatography were used to assess liver composition in fatty acyl chains and phospholipids. High-fat diet-induced obesity increased liver lipid fraction and suppressed de novo lipogenesis but did not change fatty acid esterification and saturation or insulin sensitivity. Despite a similar increase in total lipid fraction when supplementing the high-fat diet with dietary glycotoxins, impairment in the suppression of de novo lipogenesis and decreased fatty acid unsaturation and esterification were observed. Moreover, glycotoxins also decreased polyunsaturated cardiolipins and caused oxidative stress, portal inflammation, and insulin resistance in high-fat diet-induced obese rats. Dietary glycated products do not change total lipid levels in the liver of obese rats but dramatically modify the lipidemic profile, leading to oxidative stress, hepatic lipotoxicity, and insulin resistance in obesity and thus contribute to the onset of NASH.

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