Fatty Acid Supplementation Affects Skin Wound Healing in a Rat Model

Polyunsaturated fatty acids (PUFA) play an important role in reparative processes. The ratio of PUFAs n-3 to n-6 may affect wound healing. The study aimed to evaluate the effect of dietary supplementation with n-3 and n-6 PUFA in two proportions on skin wounds in laboratory rats. Adult male Wistar rats received 20% fat emulsion with a ratio of 1.4:1 (group A) or 4.3:1 (group B) for n-3:n-6 PUFAs at a daily dose of 1 mL/kg. The control group received water under the same conditions. The animals were supplemented a week before and a week after the skin excision performed on the back. The level of wound closure, various parameters of oxidative stress, and plasma fatty acids composition were evaluated. Wound tissue samples were examined by electron microscopy. The administration of fat emulsions led to significant changes in plasma polyunsaturated fatty acid composition. The increased production of reactive nitrogen species, as well as more numerous newly formed blood vessels and a greater amount of highly organized collagen fibrils in both groups A and B may indicate more intensive healing of the skin wound in rats supplemented with polyunsaturated fatty acids in high n-3:n-6 ratio.     

Methylmalonyl Coenzyme a and Fatty Acid Synthesis by Rat Liver Enzymes in Vitro

Methylmalonyl-CoA inhibited fatty acid synthesis from acetyl-CoA and malonyl-CoA by the fatty acid synthetose system in the microsomalfrec supernatant fraction of rat liver. Methylmalonyl-CoA itself was incorporated into fatty acids to produce two unusual fatty acids, which may be branched chain. These unusual fatty acids were not detected in the liver fatty acids of pigs with a vitamin B₁₂ deficiency.     

Diosgenin Ameliorated Type II Diabetes-Associated Nonalcoholic Fatty Liver Disease through Inhibiting De Novo Lipogenesis and Improving Fatty Acid Oxidation and Mitochondrial Function in Rats

Diosgenin (DIO) is a dietary and phytochemical steroidal saponin representing multiple activities. The present study investigated the protective effect of DIO on type II diabetes-associated nonalcoholic fatty liver disease (D-NAFLD). The rat model was established by high-fat diet and streptozotocin injection and then administered DIO for 8 weeks. The results showed that DIO reduced insulin resistance index, improved dyslipidemia, and relieved pancreatic damage. DIO decreased hepatic injury markers, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). H&E staining showed that DIO relieved hepatic lipid deposition. Mechanistically, DIO inhibited hepatic de novo lipogenesis (DNL) and increased fatty acid β-oxidation (FAO) through regulation of the AMPK-ACC/SREBP1 pathway. Endoplasmic reticulum (ER) stress was inhibited by DIO through regulation of PERK and IRE1 arms, which may then inhibit DNL. DIO also decreased reactive oxygen species (ROS) and enhanced the antioxidant capacity via an increase in Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx) activities. The mitochondria are the site for FAO, and ROS can damage mitochondrial function. DIO relieved mitochondrial fission and fusion disorder by inhibiting DRP1 and increasing MFN1/MFN2 expressions. Mitochondrial apoptosis was then inhibited by DIO. In conclusion, the present study suggests that DIO protects against D-NAFLD by inhibiting DNL and improving FAO and mitochondrial function.     

Position of Double Bond of Trans Isomers of Linoleic Acid Affects Fatty Acid Desaturation and Elongation

The position of the trans double bond of linoleic acid isomers affects the incorporation of the isomers in tissue lipids and their metabolic conversion to other metabolites. The 9 trans, 12 cis isomer of linoleic acid is a poor substrate and the 9 cis, 12 trans isomer is a good substrate for the enzyme that desaturates dienoic acids at position six.     

Perinatal Polyunsaturated Fatty Acid Status and Obesity Risk

High obesity rates in almost all regions of the world prompt an urgent need for effective obesity prevention. Very good scientific evidence from cell culture and rodent studies show that the availability of essential polyunsaturated fatty acids (PUFA) and their long-chain polyunsaturated derivatives, namely, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, influence adipogenesis; for this reason, early life status may influence later obesity risk. The respective PUFA effects could be mediated via their eicosanoid derivatives, their influence on cell membrane properties, the browning of white adipose tissue, changes to the offspring gut microbiome, their influence on developing regulatory circuits, and gene expression during critical periods. Randomized clinical trials and observational studies show divergent findings in humans, with mostly null findings but also the positive and negative effects of an increased n-3 to n-6 PUFA ratio on BMI and fat mass development. Hence, animal study findings cannot be directly extrapolated to humans. Even though the mechanistic data basis for the effects of n-3 PUFA on obesity risk appears promising, no recommendations for humans can be derived at present.     

Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism

Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of Bifidobacterium (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and Akkermansia accompanied by a concomitant increase of Streptococcus, Lachnospiraceae, and Paraeggerthella. The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of Clostridium, Bifidobacterium, Marvinbryantia, Butyricicoccus, and Dorea. The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.     

脂肪酸合成酶抑制剂对大鼠生长及代谢的影响

目的观察脂肪酸合成酶抑制剂浅蓝菌素对wistar大鼠生长及代谢的影响,探讨浅蓝菌素控制饮食与体重的作用机制。方法腹腔注射浅蓝菌素,测定大鼠体重及摄食的变化,同时测定血清生化指标,在试验结束后分离腹脂,并作病理学检查。结果在给药后连续7 d摄食减少40%左右,与对照组和控制摄食组比较,试验组体重显著降低(P<0.05),腹脂明显降低(P<0.01);而组织无病理学改变。血清三酰甘油下降(P<0.05),血清游离脂肪酸上升(P<0.05),血糖、尿素氮、白蛋白、球蛋白无明显改变。结论浅蓝菌素可明显抑制摄食和控制体重,是一种比较安全和有效的潜在的减肥药物。     

Dietary Omega-3 Source Effect on the Fatty Acid Profile of Intramuscular and Perimuscular Fat—Preliminary Study on a Rat Model

Fatty acids from the omega-3 family are an important element of both human and animal diets. Their activity involves a range of functions for the functioning of a whole organism, and their presence in animal diets can be considered as a means for animal origin product enrichment for human benefit or as compounds profitable for an animal’s health status. The aim of this preliminary study was to compare the effect of supplements rich in omega-3 fatty acids (linseed oil, linseed oil ethyl esters, and fish oil) in rat feed on the fatty acid profile of their intramuscular and perimuscular fat. The results demonstrated beneficial changes in fatty acid profiles (a decrease in saturated acids, an increase in unsaturated ones, i.e., omega-3 acids share) of examined tissues in the case of all supplements however, particular attention should be paid to linseed oil ethyl esters, which significantly increased the content of all omega-3 acids. Supplementation of animal diet with linseed oil ethyl esters may be beneficial for both animals, as omega-3 fatty acids exhibit profitable properties related to an animal’s health status and productivity, and humans who consume such enriched products.     

丙酸对猪肝细胞胆固醇和脂肪酸合成的影响

大鼠日粮中添加0.5%丙酸钠显著降低了血清胆固醇水平,Chen等[1]认为是易发酵纤维在大肠中的发酵产物丙酸介导了易发酵纤维降胆固醇的作用。Illeman等[2]发现18mmol/L丙酸体外灌注大鼠肝脏能显著降低肝脏胆固醇和脂肪酸的合成。Beaulieu等报道[3]经盲肠导管灌注36mmol/kg bw0.75     

幼年雌性SD大鼠营养性肥胖模型的建立

目的建立一种适合儿童肥胖研究的幼年大鼠营养性肥胖模型。方法45只刚离乳SD雌性大鼠按区组随机分为对照组、肥胖A组与B组,A组在给予普通饲料的基础上添加由黄豆芽、奶粉、猪油、鸡蛋、鱼肝油组成的高能量饲料,B组自由进食合成高脂饲料,喂养45 d后观察三组大鼠体重、Lee’s指数、腹腔内脂肪重量及其重量系数、肝脏体比、血脂、血糖、胰岛素、瘦素等肥胖相关指标。结果肥胖A组摄入的总能量及蛋白、脂肪量明显高于其他两组,A组体重4周末就明显高于对照组,6周末显著高于B组;A组的Lee’s指数、腹腔内脂肪重量及其重量系数、肝脏体比也明显高于其他两组,A组的肥胖率高于B组;但血脂、血糖、胰岛素、胰岛素敏感指数三组间无显著差异,血瘦素水平A组明显高于对照组与B组,且与体重呈正相关。结论自由进食普通饲料的基础上,每天15 g/只的高能量饲料的喂饲方式可诱导幼年雌性SD大鼠营养性肥胖模型。     

Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (−0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.     

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by ¹H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg⁻¹ i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.     

Net Synthesis of Liver Fatty Acid Synthetase in Fasted—Refed Rats

The increase in liver fatty acid synthetase that occurs on refeeding after fasting represents synthesis of new enzyme. This was demonstrated by incorporation of "C from" C-leucine into the purified enzyme, as well as by an increase in the total amount of enzyme protein isolated from the liver.     

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial

Background: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or β-oxidation. Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. Results: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. {"type":"clinical-trial","attrs":{"text":"NCT03380416","term_id":"NCT03380416"}}NCT03380416.     

硫辛酸对高脂诱导肥胖大鼠糖、脂代谢的影响

目的探讨硫辛酸（LA）对高脂诱导肥胖大鼠糖、脂代谢的影响,为防治肥胖及相关慢性疾病发生提供新措施。方法健康雄性Wistar大鼠随机分为对照组和高脂组,6周末高脂组随机分为高脂组、LA干预组（LA组）,分别用生理盐水和LA进行腹腔注射。4周后测量大鼠体重、内脏脂肪含量以及血清三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、血糖、空腹胰岛素,计算胰岛素抵抗指数（HOMA—IR）和胰岛素敏感指数（ISI）。结果与对照组比较,高脂组体重、内脏脂肪含量、血糖、胰岛素水平、血清TG和LDL水平均升高,肝、肾系数和ISI降低,差异有统计学意义（P〈0．05）。与高脂组比较,LA组体重、内脏脂肪含量和胰岛素水平降低,肝、肾系数和血清HDL水平增加,差异有统计学意义（P〈0．05）。结论LA能显著降低高脂诱导肥胖大鼠的体重和内脏脂肪含量,升高血清HDL水平,降低胰岛素水平,能明显改善高脂诱导肥胖大鼠糖、脂代谢紊乱。     

Impact of Lipid Genetic Risk Score and Saturated Fatty Acid Intake on Central Obesity in an Asian Indian Population

Abnormalities in lipid metabolism have been linked to the development of obesity. We used a nutrigenetic approach to establish a link between lipids and obesity in Asian Indians, who are known to have a high prevalence of central obesity and dyslipidaemia. A sample of 497 Asian Indian individuals (260 with type 2 diabetes and 237 with normal glucose tolerance) (mean age: 44 ± 10 years) were randomly chosen from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was assessed using a previously validated questionnaire. A genetic risk score (GRS) was constructed based on cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genetic variants. There was a significant interaction between GRS and saturated fatty acid (SFA) intake on waist circumference (WC) (P_interaction = 0.006). Individuals with a low SFA intake (≤23.2 g/day), despite carrying ≥2 risk alleles, had a smaller WC compared to individuals carrying <2 risk alleles (Beta = −0.01 cm; p = 0.03). For those individuals carrying ≥2 risk alleles, a high SFA intake (>23.2 g/day) was significantly associated with a larger WC than a low SFA intake (≤23.2 g/day) (Beta = 0.02 cm, p = 0.02). There were no significant interactions between GRS and other dietary factors on any of the measured outcomes. We conclude that a diet low in SFA might help reduce the genetic risk of central obesity confirmed by CETP and LPL genetic variants. Conversely, a high SFA diet increases the genetic risk of central obesity in Asian Indians.     

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.     

Anti-Inflammatory Effect of 4,5-Dicaffeoylquinic Acid on RAW264.7 Cells and a Rat Model of Inflammation

Anti-inflammatory agents that are safer and more effective than the currently used non-steroidal anti-inflammatory drugs are urgently needed. The dicaffeoylquinic acid (diCQA) isomer 4,5-diCQA exhibits antioxidant activity and various other health-promoting benefits; however, its anti-inflammatory properties require further investigation. This study was conducted to evaluate the anti-inflammatory properties of 4,5-diCQA in vitro and in vivo using RAW264.7 cells and a carrageenan-induced inflammation model, respectively. In RAW264.7 cells, 4,5-diCQA pretreatment significantly inhibited lipopolysaccharide-induced expression of nitric oxide, prostaglandin E₂, nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and interleukin-6, without inducing cytotoxicity. The inhibitory effects of 4,5-diCQA were mediated by the suppression of nuclear factor-κB nuclear translocation and mitogen-activated protein kinase (MAPK) phosphorylation. Oral administration of 4,5-diCQA at doses of 5, 10, and 20 mg/kg of the body weight suppressed carrageenan-induced edema and the expression of nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α in a dose-dependent manner. Collectively, our results suggest that 4,5-diCQA exerts anti-inflammatory effects by suppressing activation of the nuclear factor-κB and MAPK pathways in vitro and reducing carrageenan-induced edema in vivo. Therefore, 4,5-diCQA shows potential as a natural alternative to non-steroidal anti-inflammatory drugs.     

Fatty Acid Profile of Mature Red Blood Cell Membranes and Dietary Intake as a New Approach to Characterize Children with Overweight and Obesity

Obesity is a chronic metabolic disease of high complexity and of multifactorial origin. Understanding the effects of nutrition on childhood obesity metabolism remains a challenge. The aim of this study was to determine the fatty acid (FA) profile of red blood cell (RBC) membranes as a comprehensive biomarker of children’s obesity metabolism, together with the evaluation of their dietary intake. An observational study was carried out on 209 children (107 healthy controls, 41 who were overweight and 61 with obesity) between 6 and 16 years of age. Mature RBC membrane phospholipids were analyzed for FA composition by gas chromatography-mass spectrometry (GC-MS). Dietary habits were evaluated using validated food frequency questionnaires (FFQ) and the Mediterranean Diet Quality Index for children (KIDMED) test. Compared to children with normal weight, children with obesity showed an inflammatory profile in mature RBC FAs, evidenced by higher levels of ω-6 polyunsaturated FAs (mainly arachidonic acid, p < 0.001). Children who were overweight or obese presented lower levels of monounsaturated FA (MUFA) compared to children with normal weight (p = 0.001 and p = 0.03, respectively), resulting in an increased saturated fatty acid (SFA)/MUFA ratio. A lower intake of nuts was observed for children with obesity. A comprehensive membrane lipidomic profile approach in children with obesity will contribute to a better understanding of the metabolic differences present in these individuals.     

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

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