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The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders ( Bacteroides , Parabacteroides , Blautia , Alistipes , Romboutsia and Roseburia ). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia . A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia , Romboutsia , Ruminococcus2 , Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides , Roseburia , Butyricicoccus , Alistipes, Parasutterella , Parabacteroides and Clostridium IV . Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.

Individuals with congenital adrenal hyperplasia (CAH) require glucocorticoid therapy to replace cortisol and to control androgen excess. We sought to evaluate the effects of glucocorticoid therapy on cardiovascular and metabolic outcomes in individuals with CAH. We searched bibliographical databases through January 2016 for studies evaluating cardiovascular risk factors in individuals with CAH treated with glucocorticoids compared with controls without CAH. We used a random-effects model to synthesize quantitative data. We included 20 observational studies (14 longitudinal, six cross-sectional) with a moderate to high risk of bias. The average dose of glucocorticoids (in hydrocortisone equivalents) was 9 to 26.5 mg/m2/d. In the meta-analysis (416 patients), compared with controls without CAH, individuals with CAH had increased systolic blood pressure [weighted mean difference (WMD), 4.44 mm Hg; 95% CI, 3.26 to 5.63 mm Hg], diastolic blood pressure (WMD, 2.35 mm Hg; 95% CI, 0.49 to 4.20 mm Hg), homeostatic model assessment of insulin resistance (WMD, 0.49; 95% CI, 0.02 to 0.96), and carotid intima thickness (WMD, 0.08 mm; 95% CI, 0.01 to 0.15 mm). No statistically significant differences were noted in fasting blood glucose, insulin level, glucose, or insulin level after 2-hour glucose load or serum lipids. Data on cardiac events were sparse, and most of the literature focused on surrogate outcomes. Individuals with CAH demonstrate a high prevalence of cardiovascular and metabolic risk factors. The current evidence relies on surrogate outcomes. Long-term prospective studies are warranted to assess strategies for reducing cardiovascular risk in individuals with CAH.

ObjectiveDifferent serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question.DesignWe prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets’ effects on cholelithiasis, including HMGCR, NPC1L1, PCSK9, APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARD and PPARG.ResultsWe found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted ‘U-shaped’ relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested that HMGCR inhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis.ConclusionLower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use of HMGCR inhibitors should prevent its risk.

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers. Patients with pancreatic cancer have a poor prognosis, more research is required to identify the disease at an earlier stage. Here, the authors use lipid profiles of blood samples and show that they can distinguish patients with pancreatic cancer from healthy controls.

Alterations in lipid metabolism might contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, no pharmacological agents are currently approved in the United States or the European Union for the treatment of NAFLD. Two parallel phase 2a studies investigated the effects of liver-directed ACC1/2 inhibition in adults with NAFLD. The first study ( NCT03248882 ) examined the effects of monotherapy with a novel ACC1/2 inhibitor, PF-05221304 (2, 10, 25 and 50 mg once daily (QD)), versus placebo at 16 weeks of treatment; the second study ( NCT03776175 ) investigated the effects of PF-05221304 (15 mg twice daily (BID)) co-administered with a DGAT2 inhibitor, PF-06865571 (300 mg BID), versus placebo after 6 weeks of treatment. The primary endpoint in both studies was percent change from baseline in liver fat assessed by magnetic resonance imaging–proton density fat fraction. Dose-dependent reductions in liver fat reached 50–65% with PF-05221304 monotherapy doses ≥10 mg QD; least squares mean (LSM) 80% confidence interval (CI) was −7.2 (−13.9, 0.0), −17.1 (−22.7, −11.1), −49.9 (−53.3, −46.2), −55.9 (−59.0, −52.4) and −64.8 (−67.5, −62.0) with 16 weeks placebo and PF-05221304 2, 10, 25 and 50 mg QD, respectively. The overall incidence of adverse events (AEs) did not increase with increasing PF-05221304 dose, except for a dose-dependent elevation in serum triglycerides (a known consequence of hepatic acetyl-coenzyme A carboxylase (ACC) inhibition) in 23/305 (8%) patients, leading to withdrawal in 13/305 (4%), and a dose-dependent elevation in other serum lipids. Co-administration of PF-05221304 and PF-06865571 lowered liver fat compared to placebo (placebo-adjusted LSM (90% CI) −44.6% (−54.8, −32.2)). Placebo-adjusted LSM (90% CI) reduction in liver fat was −44.5% (−55.0, −31.7) and −35.4% (−47.4, −20.7) after 6 weeks with PF-05221304 or PF-06865571 alone. AEs were reported for 10/28 (36%) patients after co-administered PF-05221304 and PF-06865571, with no discontinuations due to AEs, and the ACC inhibitor-mediated effect on serum triglycerides was mitigated, suggesting that PF-05221304 and PF-06865571 co-administration has the potential to address some of the limitations of ACC inhibition alone. Two phase 2a trials demonstrate the efficacy of a new ACC inhibitor (PF 05221304) for reducing liver fat in patients with NAFLD, with co-administration of a DGAT2 inhibitor (PF-06865571) mitigating ACC inhibitor-mediated increases in serum triglycerides.

Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms. To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans. Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction. General community. Men and women who are overweight or have obesity (n = 61). Muffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet. Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots. By design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction. SFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Abstract Context Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. Objective The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. Data Sources We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018. Study Selection Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. Data Extraction Pairs of independent reviewers extracted data and appraised studies. Data Synthesis Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. Conclusions Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.

Nonalcoholic fatty liver disease (NAFLD) has become one of the public health problems globally. The occurrence of NAFLD is usually accompanied by a series of chronic metabolic diseases, with a prevalence rate is 25.24% among adults worldwide. Therefore, NAFLD seriously affects the quality of life in patients and causes a large economic burden. It has been reported that puerarin has the function of lowering the serum lipids, but due to the complexity of NAFLD, the specific mechanism of action has not been clarified. The aim of this study was to evaluate the preventive or ameliorating effects of two doses of puerarin (0.11% and 0.22% in diet) on high-fat and high-fructose diet (HFFD)-induced NAFLD in rats. The rats were fed with HFFD-mixed puerarin for 20 weeks. The results showed that puerarin ameliorated the levels of lipids in the serum and liver. Further exploration of the mechanism found that puerarin ameliorated hepatic lipid accumulation in NAFLD rats by reducing the expression of Srebf1 , Chrebp , Acaca , Scd1, Fasn , Acacb , Cd36 , Fatp5 , Degs1 , Plin2 , and Apob100 and upregulating the expression of Mttp , Cpt1a , and Pnpla2 . At the same time, after administration of puerarin, the levels of antioxidant markers (superoxide dismutase, glutathione peroxidase, and catalase) were significantly increased in the serum and liver, and the contents of serum and hepatic inflammatory factors (interleukin-18, interleukins-1β, and tumor necrosis factor α) were clearly decreased. In addition, puerarin could ameliorate the liver function. Overall, puerarin ameliorated HFFD-induced NAFLD by modulating liver lipid accumulation, liver function, oxidative stress, and inflammation.

Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.

To assess the efficacy of probiotic Lactobacillus on serum lipids using a meta-analysis of randomized, controlled trials. Fifteen studies containing 15 trials, with 976 subjects were included. The pooled WMD was calculated by random effects model. Probiotic Lactobacillus consumption significantly reduced TC by 0.26mmol/l (95% CI, -0.40 to -0.12) and LDL-C by 0.23mmol/l (95% CI, -0.36 to -0.10). Subgroup analysis of trials found significantly reduction of TC using L. plantarum and reduction of LDL-C using L. plantarum or L. reuteri. No significant effects were found on TG and HDL-C levels after supplementation with probiotic Lactobacillus. While, subgroup analysis found significantly beneficial effects on TG and HDL-C by consuming synbiotic food, containing L. sporogenes and inulin. Consuming probiotic Lactobacillus, especially L. reuteri and L. plantarm, could reduce TC and LDL-C significantly. The study also suggested significantly beneficial effects on TG and HDL-C by consuming synbiotic food, containing L. sporogenes and inulin.