Increase In Lipogenesis Research Articles

The Protein/Carbohydrate Ratio in the Diet Affects Zootechnical Performance and the Regulation of Intermediary Metabolism in Juveniles Tambaqui (Colossoma macropomum).

The use of carbohydrates in animal feed is a way to save protein in the diet. This study evaluated the effect of protein/starch ratio on the performance, hepatic metabolism, and body composition of juvenile tambaqui (Colossoma macropomum). Six isoenergetic experimental diets were formulated containing three levels of digestible protein (P: 230, 260 and 290 g kg- 1) and two levels of starch (S: 180 and 280 g kg- 1): P23S18, P23S28, P26S18, P26S28, P29S18 and P29S28. Juveniles tambaqui (N = 288; initial weight = 30.0 ± 3.8 g) were fed experimental diets for 90 days and the zootechnical performance was evaluated. Nine fish from each treatment group were sampled to determine somatic indices, blood metabolites, tissue energy reserves, body composition and activity of key hepatic enzymes. Blood triglycerides, hepatosomatic index, liver and muscle lipids, and hepatic glycogen increased significantly with starch while blood glucose, triglycerides and cholesterol, muscle lipids were significantly impacted by protein levels. Fish-fed S28 had increased feed intake (1714-1829 g; p < 0.0001) and fish-fed diet P26S18 had a higher protein efficiency rate (23.62%; p = 0.0356). Fish fed P23 had lower crude protein retention in the carcass (p = 0.0018) and high lipogenesis and lipid deposition in the muscle (p = 0.0069). These results suggest that dietary carbohydrates have a protein-sparing effect. Tambaqui adapted well to diets containing starch, even at higher levels, resulting in an overall increase in lipogenesis from S18 to S28. Thus, we recommend P26S18 as a cost-effective feed that ensures both zootechnical performance and quality of the final product.

Increased lipogenesis and lipidosis of gallbladder epithelium in dogs with gallbladder mucocele formation.

Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown. A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium. Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism. Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.

Increased Lipogenesis Is Important for Hexavalent Chromium-Transformed Lung Cells and Xenograft Tumor Growth

Hexavalent chromium, Cr(VI), is a known carcinogen and environmental health concern. It has been established that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to the Cr(VI)-induced carcinogenesis mechanism. However, some hallmarks of cancer remain under-researched regarding the mechanism behind Cr(VI)-induced carcinogenesis. Increased lipogenesis is important to carcinogenesis and tumorigenesis in multiple types of cancers, yet the role increased lipogenesis has in Cr(VI) carcinogenesis is unclear. We report here that Cr(VI)-induced transformation of three human lung cell lines (BEAS-2B, BEP2D, and WTHBF-6) resulted in increased lipogenesis (palmitic acid levels), and Cr(VI)-transformed cells had an increased expression of key lipogenesis proteins (ATP citrate lyase [ACLY], acetyl-CoA carboxylase [ACC1], and fatty acid synthase [FASN]). We also determined that the Cr(VI)-transformed cells did not exhibit an increase in fatty acid oxidation or lipid droplets compared to their passage-matched control cells. Additionally, we observed increases in ACLY, ACC1, and FASN in lung tumor tissue compared with normal-adjacent lung tissue (in chromate workers that died of chromate-induced tumors). Next, using a known FASN inhibitor (C75), we treated Cr(VI)-transformed BEAS-2B with this inhibitor and measured cell growth, FASN protein expression, and growth in soft agar. We observed that FASN inhibition results in a decreased protein expression, decreased cell growth, and the inhibition of colony growth in soft agar. Next, using shRNA to knock down the FASN protein in Cr(VI)-transformed BEAS-2B cells, we saw a decrease in FASN protein expression and a loss of the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells. These results demonstrate that FASN is important for Cr(VI)-transformed cell growth and cancer properties. In conclusion, these data show that Cr(VI)-transformation in vitro caused an increase in lipogenesis, and that this increase is vital for Cr(VI)-transformed cells.

Class III Alcohol Dehydrogenase Plays a Key Role in the Onset of Alcohol-Related/-Associated Liver Disease as an S-Nitrosoglutathione Reductase in Mice.

Lipid accumulation in the liver due to chronic alcohol consumption (CAC) is crucial in the development of alcohol liver disease (ALD). It is promoted by the NADH/NAD ratio increase via alcohol dehydrogenase (ADH)-dependent alcohol metabolism and lipogenesis increase via peroxisome proliferator-activated receptor γ (PPARγ) in the liver. The transcriptional activity of PPARγ on lipogenic genes is inhibited by S-nitrosylation but activated by denitrosylation via S-nitrosoglutathione reductase (GSNOR), an enzyme identical to ADH3. Besides ADH1, ADH3 also participates in alcohol metabolism. Therefore, we investigated the specific contribution of ADH3 to ALD onset. ADH3-knockout (Adh3-/-) and wild-type (WT) mice were administered a 10% ethanol solution for 12 months. Adh3-/- exhibited no significant pathological changes in the liver, whereas WT exhibited marked hepatic lipid accumulation (p < 0.005) with increased serum transaminase levels. Adh3-/- exhibited no death during CAC, whereas WT exhibited a 40% death. Liver ADH3 mRNA levels were elevated by CAC in WT (p < 0.01). The alcohol elimination rate measured after injecting 4 g/kg ethanol was not significantly different between two strains, although the rate was increased in both strains by CAC. Thus, ADH3 plays a key role in the ALD onset, likely by acting as GSNOR.

Diet-Induced Mouse Model of Nonalcoholic Steatohepatitis That Replicates the Human Disease

ObjectivesDeveloping a mouse model of nonalcoholic steatohepatitis (NASH) with obesity and fibrosis. MethodsWe fed agouti yellow male mice, which are hyperphagic, a western diet and water containing high fructose corn syrup for either 16 weeks or a year. We measured body weight and composition; we evaluated the development of NASH by histopathology and analyzed changes in gene expression by RNASeq. ResultsAfter 16 weeks, the mice had higher body weight and fat mass. The mice developed NASH with activity scores 5-6; this was confirmed by higher liver triacylglycerol content, elevated plasma ALT and AST activities, and greater hepatic infiltration by CD45-expressing leukocytes. The mice developed liver fibrosis, which was stage 1 after 16 weeks, and stage 3 after a year. Liver gene expression analysis showed increases in lipogenesis-, inflammation-, and fibrosis-related genes. Gene set enrichment analysis showed that 90% of the pathways were similarly upregulated or downregulated in the livers of mice and in human patients with NASH. ConclusionsIn this mouse model, NASH is induced with a diet similar to the average US diet, without nutritional deficiencies or hepatotoxins. NASH replicates the human disease, including the development of advanced fibrosis and very similar changes in gene expression. These similarities make this model useful for the study the pathophysiology of NASH and for preclinical studies of new drugs. Funding SourcesNIH, NSFC.

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case-control study.

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n=21) and non-cannabis users (n=16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid 13 C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched 13 C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.

The effect of high sugar diet on adipokine expression in 3T3-L1 cells and weight in mice

One of the major contributing factors to the prevalence of obesity in United States is the Western Diet, characterized by consumption of high fat and high simple sugars. Even though the issue of obesity has become a national interest, few studies have explored the relationship of high sugary diets (HSD) and obesity. The objective of this study was to determine the effects of HSD on weight gain and adipokine expression in adipose tissues. 3T3-L1 cells were cultured and differentiated in recommended differentiation medium supplemented with stock sugar solutions. Lipid accumulation was quantified with Oil Red O assay. Total RNA was isolated, first strand cDNA synthesized, and qRT-PCR performed. C57BL/6 male mice were fed normal rodent chow and water with the following sugar-sweetened beverages: fructose (10% solution), glucose (10% solution) and a combined fructose/glucose (55% fructose and 45% glucose for a 10% solution) for 16 weeks. Animal weights were recorded and water solutions were measured and replaced every two days. The in vitro data showed significant increase in lipogenesis for fructose/glucose as compared to the control. Pro-inflammatory adipokine expression of 3T3-L1 cells is significantly increased by two-fold when exposed to fructose/glucose solution. HSD-fed mice exhibited an addictive behavior with a significant increase in fructose/glucose water consumption, and weight gain. While all HSD-fed mice consumed more water and gained weight over time, the fructose/glucose and glucose groups substantially consumed more water which resulted in major weight gain. Understanding the deleterious effects of over consumption of HSD is paramount to avoiding obesity-related diseases and disorders.

FNDC4, a novel adipokine that reduces lipogenesis and promotes fat browning in human visceral adipocytes

BackgroundFibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue. MethodsPlasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study. ResultsPlasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis. ConclusionsTaken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.

The effect of high sugar diet on adipokine expression in 3T3-L1 cells and weight in mice

One of the major contributing factors to the prevalence of obesity in United States is the Western Diet, characterized by consumption of high fat and high simple sugars. Even though the issue of obesity has become a national interest, few studies have explored the relationship of high sugary diets (HSD) and obesity. The objective of this study was to determine the effects of HSD on weight gain and adipokine expression in adipose tissues. 3T3-L1 cells were cultured and differentiated in recommended differentiation medium supplemented with stock sugar solutions. Lipid accumulation was quantified with Oil Red O assay. Total RNA was isolated, first strand cDNA synthesized, and qRT-PCR performed. C57BL/6 male mice were fed normal rodent chow and water with the following sugar concentrations: fructose (10% solution), glucose (10% solution) and a combined fructose/glucose (55% fructose and 45% glucose for a 10% solution) for 16 weeks. Animal weights were recorded and water solutions were measured and replaced every two days. The in vitro data showed significant increase in lipogenesis for fructose/glucose as compared to the control. Pro-inflammatory adipokine expression of 3T3-L1 cells is significantly increased by two-fold when exposed to fructose/glucose solution. HSD-fed mice exhibited an addictive behavior with a significant increase in fructose/glucose water consumption, and weight gain. While all HSD-fed mice consumed more water and gained weight over time, the fructose/glucose group substantially consumed more water which resulted in major weight gain. Understanding the deleterious effects of over consumption of HSD is paramount to avoiding obesity-related diseases and disorders.

Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity

Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model.

Loss of Ceacam1 promotes prostate cancer progression in Pten haploinsufficient male mice

ObjectivePTEN haploinsufficiency plays an important role in prostate cancer development in men. However, monoallelic deletion of Pten gene failed to induce high prostate intraepithelial neoplasia (PIN) until Pten+/− mice aged or fed a high-calorie diet. Because CEACAM1, a cell adhesion molecule with a potential tumor suppression activity, is induced in Pten+/− prostates, the study aimed at examining whether the rise of CEACAM1 limited neoplastic progression in Pten+/− prostates. MethodsPten+/− were crossbred with Cc1−/− mice harboring a null deletion of Ceacam1 gene to produce Pten+/−/Cc1−/− double mutants. Prostates from 7-month old male mice were analyzed histologically and biochemically for PIN progression. ResultsDeleting Ceacam1 in Pten+/− mice caused an early development of high-grade PIN in parallel to hyperactivation of PI3 kinase/Akt and Ras/MAP kinase pathways, with an increase in cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and inflammation relative to Pten+/− and Cc1−/− individual mutants. It also caused a remarkable increase in lipogenesis in prostate despite maintaining insulin sensitivity. Concomitant Ceacam1 deletion with Pten+/− activated the IL-6/STAT3 signaling pathways to suppress Irf-8 transcription that in turn, led to a decrease in the expression level of promyelocytic leukemia gene, a well characterized tumor suppressor in prostate. ConclusionsCeacam1 deletion accelerated high-grade prostate intraepithelial neoplasia in Pten haploinsufficient mice while preserving insulin sensitivity. This demonstrated that the combined loss of Ceacam1 and Pten advanced prostate cancer by increasing lipogenesis and modifying the STAT3-dependent inflammatory microenvironment of prostate.

The effect of maternal dietary fat content and n-6:n-3 ratio on offspring growth and hepatic gene expression in the rat.

n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in opposition. Increasing intakes of linoleic acid (LA; n-6) v. α-linolenic acid (ALA; n-3) in Western diets has led to the hypothesis that consumption of this diet during pregnancy may be contributing to adverse offspring health. This study investigated the effects of feeding a maternal dietary LA:ALA ratio similar to that of the Western diet (9:1) compared with a proposed 'ideal' ratio (about 1:1·5), at two total fat levels (18 v. 36 % fat, w/w), on growth and lipogenic gene expression in the offspring. Female Wistar rats were assigned to one of the four experimental groups throughout gestation and lactation. Offspring were culled at 1 and 2 weeks of age for sample collection. Offspring of dams consuming a 36 % fat diet were approximately 20 % lighter than those exposed to an 18 % fat diet (P < 0·001). Male, but not female, liver weight at 1 week was approximately 13 % heavier and had increased glycogen (P < 0·05), in offspring exposed to high LA (P < 0·01). Hepatic expression of lipogenic genes suggested an increase in lipogenesis in male offspring exposed to a 36 % fat maternal diet and in female offspring exposed to a low-LA diet, via increases in the expression of fatty acid synthase and sterol regulatory element-binding protein. Sexually dimorphic responses to altered maternal diet appeared to persist until 2 weeks of age. In conclusion, whilst maternal total fat content predominantly affected offspring growth, fatty acid ratio and total fat content had sexually dimorphic effects on offspring liver weight and composition.

Inflammation Triggers Liver X Receptor-Dependent Lipogenesis.

Immune cell function can be modulated by changes in lipid metabolism. Our studies indicate that cholesterol and fatty acid synthesis increases in macrophages between 12 and 18 h after the activation of Toll-like receptors with proinflammatory stimuli and that the upregulation of lipogenesis may contribute to the resolution of inflammation. The inflammation-dependent increase in lipogenesis requires the induction of the liver X receptors, members of the nuclear receptor superfamily of transcription factors, by type I interferons in response to inflammatory signals. Instead of the well-established role for liver X receptors in stimulating cholesterol efflux, we demonstrate that liver X receptors are necessary for the proper resumption of cholesterol synthesis in response to inflammatory signals. Thus, liver X receptors function as bidirectional regulators of cholesterol homeostasis, driving efflux when cholesterol levels are high and facilitating synthesis in response to inflammatory signals. Liver X receptor activity is also required for the proper shutdown of a subset of type I interferon-stimulated genes as inflammation subsides, placing the receptors in a negative-feedback loop that may contribute to the resolution of the inflammatory response.

Pre- Probiyotikler ve Diyabet

Diabetes Mellitus, son 10 yılda prevalansı dünya çapında ciddi artış gösteren bir halk sağlığı sorunudur. Çeşitli nedenlere bağlı olarak ortaya çıkan diyabetin patogenezinde yetersiz fiziksel aktivite ve yanlış beslenme alışkanlıklarını içeren olumsuz yaşam tarzı değişikliklerine bağlı olarak meydana gelen insulin direnci ile genetik faktörlerin önemli rol oynadığı kabul gören yaygın görüşler arasındadır. Ancak son yıllarda çevresel faktörlerin de diyabet patogenezindeki etkisini gösteren kanıtlar ortaya çıkmıştır. Bu faktörlerden en çok üzerinde durulan ise mikrobiyotadır. Yürütülen çalışmalarla da mikrobiyotadaki değişen bakteri dengesinin; bağırsak geçirgenliğinde artışa, kanda Glukagon Benzeri Peptid-1 ve Glukagon Benzeri Peptid-2’nin azalmasına ve endotoksin artışına neden olduğu gösterilmiştir. Bu hormonal değişiklikler ve endotoksemi ise hedef organlarda lipogenez, yağ kütlesi, inflamasyon ve makrofaj inflitrasyonunda artış; insülin duyarlılığı, beta hücre kütlesi ve plazma insülin düzeyinde ise azalmaya neden olarak diyabetin ortaya çıkmasına katkıda bulunmaktadır. Diyabetin önüne geçebilmek ya da komplikasyonlarının oluşumunu engelleyebilmek için bağırsak mikrobiyotasında meydana gelen değişikliklerin eski haline getirilmesi ise temel amaçtır. Mikrobiyotayı düzenlemek için esas olan beslenmedir ve son yıllarda yapılan çalışmalarla prebiyotik ve probiyotik müdahaleleri ile bağırsak florasının eski haline getirilebileceği belirtilmektedir. Prebiyotikler ve probiyotiklerin diyabetik hastalarda inflamasyonu azaltmada, kan lipit profilini optimal seviyelerde tutmada, kilo kontrolünü sağlamada, antioksidan savunmayı düzeltmede, insülin duyarlılığını ve pankreas β-hücre fonksiyonlarını iyileştirerek kan şekeri regülasyonunu sağlamada etkili olduğu gösterilmiştir.

FASN AND GLUT-1 EXPRESSION IN THE PLEOMORPHIC ADENOMA AND CARCINOMA EX-PLEOMORPHIC ADENOMA

Carcinoma ex-pleomorphic adenoma (CXPA) arises in pleomorphic adenoma (PA) and with an increase in lipogenesis during its malignant transformation. The increase in lipogenesis is a feature of the cancer cells and it is characterized by the increase of fatty acid (FA) synthesis. This way, the overexpression of the enzyme fatty acid synthase (fasn) has been correlated. In the same way, the increase of glycolytic metabolism in neoplastic cells is due to the high expression of glycolytic enzymes and glucose transporters (gluts). Objective: Compare the fasn and glut-1 expression between CXPAs and PAs samples. Study Design: Forty PA and 40 CXPA were analyzed by immunohistochemistry with fasn and glut-1 antibodies. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. Results: Fifteen PA (37.5%) and 30 CXPA (75%) were fasn positive. Twenty PA (20%) and 29 CXPA (70%) were glut-1 positive. Conclusions: The present results suggest that fasn and glut-1 enzyme overexpression are associated with the malignant transformation of the PA. This way, the increase of the lipogenesis and glycolytic metabolism should be collaborative factors for carcinogenesis since cancer requires a highest demand of energy for survival and progression.

EPA and DHA have divergent effects on serum triglycerides and lipogenesis, but similar effects on lipoprotein lipase activity: a randomized controlled trial

Comparative studies suggest that DHA may have stronger serum triglyceride-lowering effects than EPA; however, the molecular basis for this differential effect remains unexplored in humans. Differential regulation of lipogenesis and triglyceride clearance are 2 possible mechanisms of action. We compared the effects of EPA and DHA supplementation on serum triglycerides, markers of lipogenesis, and lipoprotein lipase (LPL) activity in adults participating in a double-blind, multiarm, placebo-controlled parallel-group randomized trial. Lipogenesis was assessed with the lipogenic index and compound specific isotope analysis (CSIA). Young, healthy normolipidemic men and women (n=89; 21.6±0.23 y; mean ± SEM) were randomly allocated into 1 of 3 supplement groups for 12 wk: 1) olive oil, 2) ∼3 g EPA/d, and 3) ∼3 g DHA/d. Omega-3 supplements were provided in triglyceride form. Blood was collected before and after supplementation for the analysis of fatty acids and preheparin LPL activity. Variations in the 13C:12C ratio (δ13C) of palmitate (16:0) and linoleate (18:2n-6) were measured by CSIA. DHA supplementation reduced blood triglycerides (0.85±0.04 mmol/L to 0.65±0.03 mmol/L; P<0.01), with no change seen with EPA supplementation. DHA supplementation did not change the lipogenic index or δ13C-16:0, whereas EPA supplementation increased the lipogenic index by 11% (P<0.01) and δ13C-16:0 (P=0.03) from -23.2±0.2 to -22.8±0.2 milliUrey±SEM. Reduced triglyceride concentrations after DHA supplementation are associated with increased LPL activity, whereas the null effect of EPA supplementation on blood triglycerides may stem from the concomitant increases in lipogenesis and LPL activity. Further investigation of the differential triglyceride-lowering effects of EPA and DHA is warranted in both normolipidemic and hyperlipidemic individuals. This trial was registered at clinicaltrials.gov as NCT03378232.

The mechanisms involved in the increased adiposity induced by interruption of regular physical exercise practice

AimsWe investigated the effects of physical detraining on lipogenesis/lipolysis and cellularity (apoptosis/adipogenesis) in rat subcutaneous (inguinal; SC) and visceral (retroperitoneal; RP) white adipose depots. Main methodsThree groups of male Wistar rats (6-wk old) were studied: (1) (T) trained for 12 weeks; (2) (D) trained for 8 weeks and detrained for 4 weeks; and (3) (S) age-matched sedentary. Training consisted of treadmill running sessions (1 h/day, 5 days/week, 50–60% maximal race capacity). Key findingsPhysical detraining increased glucose oxidation, lipogenesis, and adipocyte size in the SC and RP depots. The number of apoptotic SC adipocytes was reduced by 53% in the T (p < 0.0001) and by 43% in the D (p < 0.001) as compared with S. RP adipocyte apoptosis in the T and D was 9.48% and 10.9% greater compared to the S, respectively (p < 0.05). In the SC stromal vascular fraction (SVF) of D rats, adiponectin, sterol regulatory element binding protein (SREBP)-1c, Peroxisome proliferator-activated receptor gamma (PPARγ), and Perilipin A mRNA expressions were more pronounced than S group, suggesting a more intense adipogenesis. This putative adipogenic effect was not observed in the RP depot. The physical detraining promoted rapid increase in the SC and RP depots however not through the same mechanisms. SignificancePhysical detraining induced fat cell hypertrophy (increase of lipogenesis) in both SC and RP whereas hyperplasia (increase of adipogenesis and reduction of apoptosis) was found in SC only. These results indicate the mechanism associated with obesogenic effects of detraining varies with the fat depot.

Carnosic Acid Modulates Increased Hepatic Lipogenesis and Adipocytes Differentiation in Ovariectomized Mice Fed Normal or High-Fat Diets.

As postmenopausal women experience a rapid increase in cardiovascular disease (CVD) risk with an increase in abdominal fat, dietary interventions to reduce CVD risk have been emphasized. This study was aimed at investigating the effect of a high-fat diet (HFD) in combination with an ovariectomy on liver and adipose tissue fat metabolism. The efficacy of carnosic acid (CA) supplementation in the suppression of HFD- and ovariectomy-induced obesity was also evaluated. Ovariectomized (OVX) or sham-operated mice at eight weeks of age were fed with a normal diet (ND), HFD, ND and 0.02% CA, or HFD and 0.02% CA for 12 weeks. All of the animals were sacrificed at the age of 20 weeks. The blood and tissue markers of the lipogenesis and adipocyte differentiation were measured. As expected, ovariectomy decreased the uterus weight and serum 17β-estradiol concentration. The HFD and ovariectomy significantly contributed to increases in the body weight and total fat mass, which were effectively inhibited by CA supplementation. The circulating concentrations of insulin, leptin, and TG (triglyceride) were significantly higher in the HFD group, and the concentrations were two to five times higher in the OVX and HFD group compared with those of the ND group. The CA supplementation significantly lowered the insulin, leptin, and TG concentrations in the OVX and HFD mice. The hepatic protein expressions of pAMPK and pACC were up-regulated by CA supplementation in OVX mice fed either ND or HFD. The expressions of hepatic SREBP1c and FAS mRNA were the highest in the OVX and HFD group, which were suppressed by CA supplementation. The adipose tissue PPARγ, aP2, and lipoprotein lipase (LPL) mRNA expressions were up-regulated by a HFD or ovariectomy, while they were significantly reduced in the mice fed a CA supplemented diet. The TNF-α and IL-6 mRNA levels in the adipose tissue were decreased by providing CA in the OVX groups. These results suggest that HFD and ovariectomy independently contribute to body fat accumulation, and CA effectively alleviated the ovariectomy-induced increases in lipogenesis and adipocyte differentiation. Further human trials are required in order to evaluate the efficacy of rosemary-derive CA as natural anti-adipogenic compounds, especially in postmenopausal women.

Lipid deposition pattern and adaptive strategy in response to dietary fat in Chinese perch (Siniperca chuatsi)

BackgroundPrevious studies in teleost have demonstrated the adaptive strategy to maintain hepatic lipid homeostasis within certain limit. The excess of fat-intake could induce abnormal lipid deposition in liver but not adipose tissue. However, the molecular mechanism between the impaired lipid homeostasis and the aggravated lipid deposition in liver has not been elucidated well in fish.MethodsFour isonitrogenous diets with different fat levels (2, 7, 12 and 17%) were formulated, named L2, L7, L12 and L17 respectively, and fed Chinese perch (44.50 ± 0.25 g) to apparent satiation for five weeks. Growth index, triglyceride concentrations and expression of genes involved in lipid metabolism were measured.ResultsThe maximal growth performance and food intake were observed in L12 group. The lipid content in liver and serum were comparable in L2, L7 and L12 groups, while they were increased significantly in L17 group. Histology analysis also demonstrated that mass lipid droplets emerged in hepatocyte and then induced hepatic steatosis in L17 group. Compared to L2 group, the lipolytic genes related to fatty acids (FAs) transport (lpl & hl) and FAs β-oxidation (cpt1 & cs) were increased in L7 and L12 group. Relative mRNA levels of the gluconeogenesis (pc, pepck & g6pase) were also increased, in contrast, the lipogenic genes (srebp1, accα & fas) were decreased. Compared to L12 group, L17 group had higher mRNA levels of the FAs transport and the lipogenesis. But the lipolytic genes related to FAs β-oxidation were steady and the mRNA levels of gluconeogenesis were down-regulated instead.ConclusionsWithin certain limit, the increase of dietary fat in L7 and L12 group was propitious to reduce the consumption of protein and improve growth performance in Chinese perch. It was due to the homeostasis of hepatic triglyceride (TG) pool and serum glucose through promoting the FAs β-oxidation and gluconeogenesis respectively. Both the increase of lipogenesis and the absence of FAs β-oxidation in L17 group could trigger the esterification of FAs, indeed, the inhibition of gluconeogenesis could also aggravate triglyceride accumulation in liver and induce hepatic steatosis.

The Antidiabetic Drug Lobeglitazone Protects Mice From Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked with type II diabetes (T2D). The progression of NAFLD is associated with the induction of lipogenesis through hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used as an antidiabetic drug to lower serum glucose level through an increase in insulin sensitivity. It is known to improve pathological symptoms in animals and humans with NAFLD. However, the underlying molecular mechanism of the protective effects of lobeglitazone against NAFLD has not been elucidated. Here, we show that under the physiological condition of acute lipogenesis, lobeglitazone inhibits hepatic lipid synthesis, the subsequent ER stress, and ω-oxidation of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone protected mice from lipogenesis-induced oxidative liver injury. Taken together, lobeglitazone might be a suitable drug for the treatment of patients with diabetes and NAFLD.