Lipidomics reveals ceramide biomarkers for detecting central precocious puberty in girls.

BACKGROUND: Pubertal timing is modulated by complex interactions between the pituitary and gonadal sex steroid hormones. Evidence indicates that sphingolipids are involved in the biosynthesis of steroid hormones at multiple levels. METHOD: This study recruited adolescent female patients from pubertal and pediatric endocrine clinics in Northern and Southern Taiwan from the Taiwan Puberty Longitudinal Study. A total of 112 plasma samples (22 healthy control, 29 peripheral precocious puberty (PPP), and 61 CPP samples) were collected. We extracted lipids from the plasma samples using the modified Folch method. The un-targeted ultrahigh-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed for the lipid analysis. RESULTS: We identified sphingolipid-linked metabolites, including Cer(18:0/15:0), Cer(18:1/16:0), and Cer(18:1/26:0) as candidate biomarkers for distinguishing girls with CPP from the control group by using an excellent discrimination model (AUC = 0.964). Moreover, Cer(18:0/22:0) and Cer(d18:0/18:1) were identified as potential biomarkers of PPP, with an AUC value of 0.938. Furthermore, CerP(18:1/18:0) was identified as the sole candidate biomarker capable of differentiating CPP from PPP. CONCLUSIONS: The biomarkers identified in this study can facilitate the accurate detection of CPP in girls, provide insights into lipid-linked pathophysiology, and present a novel method of monitoring the progression of this disorder.

Essential trace element and phosphatidylcholine remodeling: Implications for body composition and insulin resistance.

BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Melatonin Ameliorates Neuropsychiatric Behaviors, Gut Microbiome, and Microbiota-Derived Metabolites in Rats with Chronic Sleep Deprivation.

With the increasing prevalence of sleep deprivation (SD)-related disorders, the effective treatment of sleep disorders has become a critical health research topic. Thus, we hypothesized and investigated the effectiveness of a 3-week melatonin intervention on neuropsychiatric behavioral responses mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Eighteen 6-week-old Wistar rats were used and divided into the control grup (C, n = 6), SD group (n = 6), and melatonin-supplemented group (SDM, n = 6). During weeks 0 to 6, animals were provided with the AIN-93M diet and free access to water. Four-week chronic SD was conducted from weeks 7 to 10. Exogenous melatonin administration (10 mg/kg BW) was injected intraperitoneally 1 h before the daily administration of SD for 3 weeks in the SDM group. SD rats exhibited anxiety-like behavior, depression-like behavior, and cognitive impairment. Exogenous melatonin administration ameliorated neuropsychiatric behaviors induced by chronic SD. Analysis of fecal metabolites indicated that melatonin may influence brain messaging through the microbiota-gut-brain axis by increasing the production of short-chain fatty acids (SCFA) and decreasing the production of secondary bile acids (SBA). Four-week SD reduced the cerebral cortex expression of MT1, but not in the colon. Chronic SD led to anxiety and depression-like behaviors and cognitive decline, as well as the reduced intestinal level of SCFAs and the enhanced intestinal level of SBAs in rats. In this work, we confirmed our hypothesis that a 3-week melatonin intervention on neuropsychiatric behavioral response mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD.

Attenuation of Chronic Stress-Induced Depressive-like Symptoms by Fish Oil via Alleviating Neuroinflammation and Impaired Tryptophan Metabolism in Aging Rats.

The prevalence of depression is increasing, and geriatric depression, in particular, is difficult to recognize and treat. Depression in older adults is often accompanied by neuroinflammation in the central nervous system (CNS). Neuroinflammation affects the brain's physiological and immune functions through several pathways and induces depressive symptoms. This study investigated the relationship among depression, neuroinflammation, and fish oil supplementation. Thirty-six male Sprague-Dawley rats were used in an aging-related depression animal model to simulate geriatric depression. Cognitive function, depressive-like symptoms, peripheral nervous system and CNS inflammation status, and the tryptophan-related metabolic pathway were analyzed. The geriatric depression animal model was associated with depressive-like behaviors and cognitive impairment. The integrity of the blood-brain barrier was compromised, resulting in increased expression of ionized calcium-binding adapter molecule 1 and the glial fibrillary acidic protein in the brain, indicating increased neuroinflammation. Tryptophan metabolism was also negatively affected. The geriatric-depressive-like rats had high levels of neurotoxic 5-hydroxyindoleacetic acid and kynurenine in their hippocampus. Fish oil intake improved depressive-like symptoms and cognitive impairment, reduced proinflammatory cytokine expression, activated the brain's glial cells, and increased the interleukin-10 level in the prefrontal cortex. Thus, fish oil intervention could ameliorate abnormal neurobehaviors and neuroinflammation and elevate the serotonin level in the hippocampus.

Modulatory effect of n-3 polyunsaturated fatty acids on depressive-like behaviors in rats with chronic sleep deprivation: potential involvement of melatonin receptor pathway and brain lipidome.

Clinical evidence suggests that a bidirectional relationship is present between sleep loss and psychiatric disorders. Both melatonin receptor agonist ramelteon (RMT) and n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit antidepressant effects, while their underlying molecular mechanisms might be different. Thus, the present study aims to investigate the add-on effects and possible mechanisms of how RMT and different n-3 PUFAs modulate the melatonin receptor pathway as well as brain lipidome to ameliorate the neuropsychiatric behaviors displayed in rats under chronic sleep deprivation. Thirty-one 6-week-old male Wistar rats were divided into five groups: control (C), sleep deprivation (S), sleep deprivation treated with RMT (SR), sleep deprivation treated with RMT and eicosapentaenoic acid (C20:5n-3, EPA) (SRE), and sleep deprivation treated with RMT and docosahexaenoic acid (C22:6n-3, DHA) (SRD) groups. The results reveal that RMT plus EPA alleviated depressive-like behavior when the rats were subjected to the forced swimming test, whereas RMT plus DHA alleviated anxiety-like behavior when the rats were subjected to the elevated plus maze test. The results of a western blot analysis further revealed that compared with the rats in the S group, those in the SRE and SRD groups exhibited a significantly increased expression of MT2 in the prefrontal cortex, with greater benefits observed in the SRE group. In addition, decreased BDNF and TrkB expression levels were upregulated only in the SRE group. Lipidomic analysis further revealed possible involvement of aberrant lipid metabolism and neuropsychiatric behaviors. RMT plus EPA demonstrated promise as having the effects of reversing the levels of the potential biomarkers of depressive-like behaviors. RMT plus EPA or DHA could ameliorate depressive- and anxiety-like behaviors in sleep-deprived rats through the alteration of the lipidome and MT2 receptor pathway in the brain, whereas EPA and DHA exerted a differential effect.

Effects of Resveratrol on Muscle Inflammation, Energy Utilisation, and Exercise Performance in an Eccentric Contraction Exercise Mouse Model.

Eccentric contraction can easily cause muscle damage and an inflammatory response, which reduces the efficiency of muscle contraction. Resveratrol causes anti-inflammatory effects in muscles, accelerates muscle repair, and promotes exercise performance after contusion recovery. However, whether resveratrol provides the same benefits for sports injuries caused by eccentric contraction is unknown. Thus, we explored the effects of resveratrol on inflammation and energy metabolism. In this study, mice were divided into four groups: a control group, an exercise group (EX), an exercise with low-dose resveratrol group (EX + RES25), and an exercise with high-dose resveratrol group (EX + RES150). The results of an exhaustion test showed that the time before exhaustion of the EX + RES150 group was greater than that of the EX group. Tumour necrosis factor-α (Tnfα) mRNA expression was lower in the EX + RES150 group than in the EX group. The energy utilisation of the EX + RES150 group was greater than that of the EX + RES25 group in different muscles. High-dose resveratrol intervention decreased Tnfα mRNA expression and enhanced the mRNA expressions of sirtuin 1, glucose transporter 4, AMP-activated protein kinase α1, and AMP-activated protein kinase α2 in muscles. These results revealed that high-dose resveratrol supplementation can reduce inflammation and oxidation and improve energy utilisation during short-duration high-intensity exercise.

N-3 PUFA Ameliorates the Gut Microbiota, Bile Acid Profiles, and Neuropsychiatric Behaviours in a Rat Model of Geriatric Depression.

The brain-gut-microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota-bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms. Sprague Dawley rats were fed a fish oil diet and administered D-galactose combined with chronic unpredictable mild stress (CUMS) to simulate geriatric depression. The cognitive function, psychological symptoms, microbiota compositions, and faecal bile acid profiles of the rats were assessed thereafter. A correlation analysis was conducted to determine whether the fish oil-induced alteration of the rats' microbiota and bile acid profiles affected the rats' behaviour. D-galactose and CUMS resulted in lower concentrations of Firmicutes, significantly altered bile acid profiles, and abnormal neurobehaviours. Fish oil intake alleviated the rats' emotional symptoms and increased the abundance of Bacteroidetes, Prevotellaceae, Marinifilaceae, and Bacteroidesuniformis. It also elevated the concentrations of primary bile acids and taurine-conjugated bile acids in the rats' faeces. The rats' taurine-conjugated bile acid levels were significantly correlated with their behavioural outcomes. In short, fish oil intake may alleviate psychological symptoms by altering the microbial metabolites involved in the BGM axis, especially in the conjugation of bile acids.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

High-dose ferric citrate supplementation attenuates omega-3 polyunsaturated fatty acid biosynthesis via downregulating delta 5 and 6 desaturases in rats with high-fat diet-induced obesity.

Obesity is associated with an increased risk of an iron deficiency; however, a synergistic relationship between iron and lipid homeostasis was also observed. The aim of this study was to investigate the effects of pharmacological doses of iron supplementation on omega 3 (n-3) and omega 6 (n-6) polyunsaturated fatty acids (PUFAs). Sprague-Dawley (SD) rats were fed a normal diet or a 50% high-fat diet (HFD) without or with pharmacological doses of ferric citrate (0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks, and erythrocyte profiles of n-3 and n-6 PUFAs were quantitated. Ferric citrate supplementation showed dose-related effects on liver inflammation, liver iron accumulation, and increasing circulating levels of iron, erythrocyte degradation biomarkers LVV-hemorphin-7, malondialdehyde (MDA), and insulin. Obese rats supplemented with 2 g ferric iron per kg diet also had decreased levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and total n-3 PUFAs compared to rats fed a normal diet or HFD alone. A western blotting analysis revealed that iron-mediated downregulation of n-3 PUFA-converting enzymes (Δ5 and Δ6 desaturases) only occurred at high dosages (≥1 g ferric iron per kg diet). A Spearman correlation analysis showed that total liver iron and serum LVV-hemorphin-7 and MDA were negatively correlated with n-3 PUFAs and their converting enzymes (Δ5 and Δ6 desaturases) (all p < 0.05). In conclusion, obese rats that received high-dose ferric citrate supplementation (>1 g of ferric iron per kg diet) exhibited decreased n-3 PUFA levels via downregulation of expressions of Δ5 and Δ6 desaturase enzymes.

New Insights into Depressive Disorder with Respect to Low-Grade Inflammation and Fish Oil Intake.

Unipolar depression has been recognized as one of the major diseases by the World Health Organization in the 21st century. The etiology of depression is complicated and includes genetic factors, stress, aging, and special physical status (pregnancy, metabolic syndrome, and trauma). Numerous animal and human studies have demonstrated that n-3 polyunsaturated fatty acids (n-3 PUFAs) are highly correlated to cognition and depression. These nutritional antidepressants, including EPA and DHA, have a range of neurobiological activities contributing to their potential antidepressant effects. Our preclinical and clinical studies have indicated that n-3 PUFA supplementation in addition to standard antidepressant medications may provide synergistic neuroprotective and antioxidant/inflammatory effects. To translate our preliminary findings into clinical application, this paper reviews the existing evidence on the antidepressant effects of n-3 PUFAs and the potential underlying mechanisms, which include modulation of chronic lowgrade inflammation and the corresponding changes in peripheral blood immune biomarkers.

Eicosapentaenoic Acid Inhibits KRAS Mutant Pancreatic Cancer Cell Growth by Suppressing Hepassocin Expression and STAT3 Phosphorylation.

BACKGROUND: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. METHODS: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. RESULTS: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. CONCLUSIONS: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

Nutrient Intake through Childhood and Early Menarche Onset in Girls: Systematic Review and Meta-Analysis.

Among the genetic and environmental risk factors, nutrition plays a crucial role in determining the timing of puberty. Early menarche onset (EMO) is defined as when girls reach menarche onset at an age which is earlier than the mean/median age of menarche, between 12 and 13 years of age, according to individual ethnicity. The present study examined the association between nutrient intake in childhood and EMO risk in healthy girls by performing a systematic review and meta-analysis of prospective studies. We screened EMBASE, Cochrane Library, PubMed/MEDLINE, and Web of Science databases for 16 eligible studies with all medium-to-high quality scores ranging from 3 to 5 of 6 possible points with 10,884 subjects. Higher intakes of energy (risk ratio (RR) = 3.32, 95% confidence interval (CI) = 1.74-6.34, I2 = 97%), and protein (RR = 3.15, 95% CI = 2.87-3.44, I2 = 0%) were associated with EMO risk. For each additional 1 g/day animal protein intake in childhood, the age at menarche was approximately two months earlier (ß = -0.13, I2 = 55%), and high iron intake was associated with EMO (RR = 1.20, 95% CI = 1.03-1.40, I2 = 0%). Polyunsaturated fatty acid (PUFAs) intake was associated with EMO risk with a dose-response effect (RR = 1.25, 95% CI = 1.05-1.49, I2 = 44%). Girls with a high intake of fiber and monosaturated fatty acids (MUFAs) in childhood experienced later menarche onset (RR = 0.83, 95% CI = 0.69-1.00, I2 = 31%; RR = 0.66, 95% CI = 0.50-0.86, I2 = 0%, respectively). Thus, adherence to a high intake of animal proteins-, iron- and PUFA-rich food diet makes girls more likely to have EMO, while a high intake of fiber- and MUFA-rich foods may protect girls from EMO. Further studies are expected to investigate the role of specific types of PUFAs and MUFAs on EMO to promote healthy sexual maturity in girls.

Degree of lipid saturation affects depressive-like behaviour and gut microbiota in mice.

This study explored the effects of the degree of lipid saturation on depressive behaviour and gut microbiota in mice. Thirty-two mice were divided into normal (N), Prozac (NP), lard (L) and fish oil (F) groups. After a 12-week dietary intervention, the open field test (OFT) and the forced swim test (FST) were conducted before sacrifice. The mice in the L group exhibited anxiety-like behaviours in the OFT and depressive-like behaviours in the FST. A significant difference was observed in ß-diversity indices between the L group and the F group. The abundance of Allobaculum and Bifidobacterium was significantly higher in the F group than in the L and N groups. The prefrontal cortex fatty acid composition was altered in various lipid-treated groups and was highly correlated with depressive-like behaviours. In conclusion, the degree of lipid saturation affects depressive-like behaviour, gut microbiota composition, and the prefrontal cortex fatty acid profile in mice.

Rice Bran Reduces Weight Gain and Modulates Lipid Metabolism in Rats with High-Energy-Diet-Induced Obesity.

Obesity has become an epidemic worldwide. It is a complex metabolic disorder associated with many serious complications and high morbidity. Rice bran is a nutrient-dense by product of the rice milling process. Asia has the world's highest rice production (90% of the world's rice production); therefore, rice bran is inexpensive in Asian countries. Moreover, the high nutritional value of the rice bran suggests its potential as a food supplement promoting health improvements, such as enhancing brain function, lowering blood pressure, and regulating pancreatic secretion. The present study evaluated the anti-obesity effect of rice bran in rats with high-energy diet (HED)-induced obesity. Male Sprague-Dawley rats were randomly divided into one of five diet groups (n = 10 per group) and fed the following for eight weeks: Normal diet with vehicle treatment, HED with vehicle, rice bran-0.5X (RB-0.5X) (2% wt/wt rice bran), RB-1.0X (4% wt/wt rice bran), and RB-2.0X (8% wt/wt rice bran). Rice bran (RB-1.0X and RB-2.0X groups) markedly reduced obesity, including body weight and adipocyte size. In addition, treating rats with HED-induced obesity using rice bran significantly reduced the serum uric acid and glucose as well as the liver triglyceride (TG) and total cholesterol (TC). Furthermore, administration of an HED to obese rats significantly affected hepatic lipid homeostasis by increasing phosphotidylcholine (PC; 18:2/22:6), diacylglycerol (DG; 18:2/16:0), DG (18:2/18:1), DG (18:1/16:0), cholesteryl ester (CE; 20:5), CE (28:2), TG (18:0/16:0/18:3), and glycerol-1-2-hexadecanoate 3-octadecanoate. However, the rice bran treatment demonstrated an anti-adiposity effect by partially reducing the HED-induced DG (18:2/18:1) and TG (18:0/16:0/18:3) increases in obese rats. In conclusion, rice bran could act as an anti-obesity supplement in rats, as demonstrated by partially reducing the HED-induced DG and TG increases in obese rats, and thus limit the metabolic diseases associated with obesity and the accumulation of body fat and hepatic lipids in rats.

Fish Oil, but Not Olive Oil, Ameliorates Depressive-Like Behavior and Gut Microbiota Dysbiosis in Rats under Chronic Mild Stress.

BACKGROUND: This study investigated the effects of fish oil and olive oil in improving dysbiosis and depressive-like symptoms. METHODS AND RESULTS: Male rats were fed normal, fish oil-rich or olive oil-rich diets for 14 weeks. Chronic mild stress (CMS) was administered from week 2. The sucrose preference test (SPT) and forced swimming test (FST) were used to determine depressive-like behavior. The SPT results revealed that the CMS, CMS with imipramine (CMS+P) treatment, and CMS with olive oil diet (CMS+O) groups exhibited significantly reduced sucrose intake from week 8, whereas the fish oil diet (CMS+F) group exhibited significantly reduced sucrose intake from week 10. The FST results showed that the immobile time of the CMS+F group was significantly less than that of the CMS-only group. Next generation sequencing (NGS) results showed CMS significantly reduced the abundance of Lactobacillus and increased that of Marvinbryantia and Ruminiclostridium_6. However, the CMS+F group showed an increase in the abundance of Eisenbergiella, Ruminococcaceae_UCG_009, and Holdemania, whereas the CMS+O group showed an increase in the abundance of Akkermansia. CONCLUSIONS: CMS stimuli altered the gut microbiome in depressed rats. Fish oil and olive oil exerted part of a prebiotic-like effect to ameliorate dysbiosis induced by CMS. However, only fish oil ameliorated depressive-like symptoms.

Effects of Caloric Restriction with Protein Supplementation on Plasma Protein Profiles in Middle-Aged Women with Metabolic Syndrome-A Preliminary Open Study.

BACKGROUND: Clinical studies have demonstrated that higher protein intake based on caloric restriction (CR) alleviates metabolic abnormalities. However, no study has examined the effects of plasma protein profiles on caloric restriction with protein supplementation (CRPS) in metabolic syndrome (MetS). Therefore, using a proteomic perspective, this pilot study investigated whether CRPS ameliorated metabolic abnormalities associated with MetS in middle-aged women. METHODS: Plasma samples of middle-aged women with MetS in CR (n = 7) and CRPS (n = 6) groups for a 12-week intervention were obtained and their protein profiles were analysed. Briefly, blood samples from qualified participants were drawn before and after the dietary treatment. Anthropometric, clinical, and biochemical variables were measured and correlated with plasma proteomics. RESULTS: In results, we found that body mass index, total body fat, and fasting blood glucose decreased significantly after the interventions but were not different between the CR and CRPS groups. After liquid chromatography⁻tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. These proteins are involved in inflammation, the immune system, and coagulation responses. Moreover, blood low-density lipoprotein cholesterol levels were significantly and positively correlated with C6 plasma levels in both groups. CONCLUSIONS: These findings suggest that CRPS improves inflammatory responses in middle-aged women with MetS. Specific plasma protein expression (i.e., A2M, C4BPA, C1RL, C6, C8G, and PROS) associated with the complement system was highly correlated with fasting blood glucose (FBG), blood lipids (BLs), and body fat.

A high linoleic acid diet exacerbates metabolic responses and gut microbiota dysbiosis in obese rats with diabetes mellitus.

Dietary polyunsaturated fatty acid (PUFA) levels may affect inflammatory responses and lipid metabolism. Gut microbiota diversity is strongly associated with chronic inflammatory disease, diabetes mellitus (DM), and obesity through abnormal energy homeostasis. In this study, the association between metabolic responses and gut microbiota diversity at different dietary n-6/n-3 PUFA ratios was evaluated in DM rats. Obesity and DM were induced in rats by using a high-fat diet and streptozotocin (STZ), respectively. The obese DM rats were assigned to three groups and administered regular (R), high (H), and low (L) n-6/n-3 ratio diets (n-6/n-3 = 6.39, 3.02, and 9.29, respectively) for 6 weeks. Some metabolic parameters and gut microbiota of the rats were analysed. The results revealed that a high linoleic acid diet increased the plasma and kidney interleukin 6 levels, whereas a low n-6/n-3 ratio diet ameliorated blood glucose homeostasis, reduced plasma tumour necrosis factor α levels, and inhibited systematic inflammation. DM rats exhibited low gut microbiota diversity; however, compared with the R group, the L and H groups did not exhibit alterations in the α-diversity (Observed, Chao 1, Shannon and Simpson). The percentage of Firmicutes was lower in the DM groups than in the non-DM group; however, the L group showed a nonsignificantly higher Firmicutes/Bacteroidetes ratio than did the other groups. Thus, a low n-6/n-3 ratio diet can improve blood glucose homeostasis, reduce systematic inflammation, ameliorate glomerular basal membrane thickening, reduce the expression of receptors of advanced glycation end products in renal vessel walls, and prevent diabetic nephropathies.