Increased Serum High-density Lipoprotein Cholesterol Research Articles

Beneficial effects of oleanolic acid on hepatopancreas oxidative stress and intestinal microbiota structure of red swamp crayfish (Procambarus clarkia)

This study aimed to evaluate the beneficial effects of oleanolic acid (OA) in the culture of red swamp crayfish (Procambarus clarkia) by investigating the impact of dietary OA on growth performance, hepatopancreas antioxidant activity, innate immunity, and intestinal microbiota structure. An eight-week feeding trial was conducted using different dietary OA concentrations: 0, 250, 500, 750, and 1000 mg·kg–1. The results revealed that the groups with 500–1000 mg·kg–1 OA exhibited increased final body weight, weight gain rate, and specific growth rate, as well as decreased feed conversion ratio compared to those in the control group (P < 0.05). Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities showed a linear decrease with increasing dietary OA concentration. OA demonstrated hypolipidemic effects by reducing serum glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, while increasing serum high-density lipoprotein cholesterol levels (P < 0.05). OA500 to OA1000 groups exhibited significantly higher trypsin activity compared to that of the control, while lipase activity linearly decreased with increasing dietary OA concentration. The antioxidant capacity, as indicated by glutathione level in the hepatopancreas, showed significant differences between the OA treatment group and the control group. However, dietary OA did not significantly alter the structure of the intestinal microbiota. These findings suggest that dietary OA supplementation effectively improves the growth performance and enhanced the innate immunity of crayfish. Furthermore, OA significantly promotes the antioxidant capacity, thereby protecting the hepatopancreas from oxidative damage. The optimal dose range of dietary OA for application in crustacean culture is recommended to be between 500 and 1000 mg·kg−1.

Impacts of dietary lipids derived from animal or vegetable sources on healthy rats

ABSTRACT This study sought to assess the health impact of feeding adult healthy rats with either 7% (w/w) animal-derived fat (subcutaneous rump fat or peri-kidney fat) from domestic buffalo or vegetable oil (corn oil or olive oil) for 8 weeks on bioactivity; lipid profile; hepatic and cardiac histological changes. Twenty-four male albino rats were randomly categorized into four dietary groups (six rats/group): 1) diet contains 7% (w/w) corn oil; 2) diet contains 7% (w/w) olive oil; 3) diet contains 7% (w/w) subcutaneous rump fats and 4) diet contains 7% (w/w) Peri-kidney fats. Animal fats intake significantly increased serum total lipids (TL), triacylglycerol (TG), low-density lipoprotein cholesterol (LDLC), cardiac troponin-I (CTn-I) concentration as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) activities compared to vegetable oils intake. In histopathological research, liver and heart sections excised from rats consumed animal-derived fats showed several signs of extensive damage, including inflammation as well as fibrosis. Compared to animal-derived fats, vegetable oils consumption markedly increased serum high-density lipoprotein cholesterol (HDLC) concentration and exhibited a potential attenuation effect on liver and heart enzymes activities and a potential role in the reduction of TG in the bloodstream of rats as well as revealed normal liver and heart histopathological architectures. In conclusion, this study suggests that, replacing animal fats, especially peri-kidney fat with vegetable oils, particularly olive oil in diets, liver and heart can be protected.

Dietary grape seed proanthocyanidin extract supplementation improves antioxidant capacity and lipid metabolism in finishing pigs

Grape seed proanthocyanidin extract (GSPE) plays a significant role in body health, including improving antioxidant capacity and maintaining lipid metabolism stability. However, whether dietary GSPE supplementation can improve lipid metabolism in finishing pigs remains unclear. Here 18 castrated male Duroc × Landrace × Yorkshire finishing pigs were randomly divided into three groups with six replicates and one pig per replicate. Pigs were fed a basal diet (control), a basal diet supplemented with 100 mg/kg GSPE, or a basal diet supplemented with 200 mg/kg GSPE for 30 days. Antioxidant analysis showed that dietary 200 mg/kg GSPE supplementation increased glutathione, total antioxidant capacity and glutathione peroxidase levels, and reduced malondialdehyde levels in serum, muscle and liver. Dietary 200 mg/kg GSPE supplementation also upregulated the mRNA and protein levels of nuclear-related factor 2 (Nrf2). Lipid metabolism analysis showed that dietary GSPE supplementation increased serum high-density lipoprotein cholesterol levels and reduced serum triglyceride and total cholesterol levels. Besides, GPSE upregulated the mRNA expression of lipolysis- and fatty acid oxidation-related genes downregulated the mRNA expression of lipogenesis-related genes, and activated the AMPK signal in finishing pigs. Together, we provided evidence that dietary GSPE supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.

Partial replacement of high-fat diet with n-3 PUFAs enhanced beef tallow attenuates dyslipidemia and endoplasmic reticulum stress in tunicamycin-injected rats.

Metabolic syndrome (MetS) is considered as a complex, intertwined multiple risk factors that directly increase the risk of various metabolic diseases, especially cardiovascular atherosclerotic diseases and diabetes mellitus type 2. While lifestyle changes, including dietary intervention are effective in mitigating or preventing MetS, there are no specific therapies against MetS. Typical western diets comprise of high saturated fatty acid, cholesterol, and simple sugar; consequently their consumption may increase the potential pathological developmental risk of MetS. Partial replacement of dietary fatty acids with polyunsaturated fatty acids (PUFAs) is widely recommended measure to manage MetS-related disorders. In the present study, we used rat model to investigate the role of n-3 PUFA enriched beef tallows (BT) on MetS and tunicamycin (TM)-induced endoplasmic reticulum (ER) stress, by partially replacing dietary fat (lard) with equal amounts of two different BTs; regular BT or n-3 PUFA-enriched BT. The experimental rats were randomly assigned to three different dietary groups (n = 16 per group): (1) high-fat and high-cholesterol diet (HFCD); (2) HFCD partially replaced with regular BT (HFCD + BT1); (3) HFCD partially replaced with n-3 enhanced BT (w/w) (HFCD + BT2). After 10 weeks of dietary intervention, each experimental rodent was intraperitoneally injected with either phosphate-buffered saline or 1 mg/kg body weight of TM. HFCD + BT2 showed improved dyslipidemia before TM injection, and increased serum high-density lipoprotein cholesterol (HDL-C) levels after TM injection. BT replacement groups had significantly reduced hepatic triglyceride (TG) levels, and decreased total cholesterol (TC) and TG levels in epididymal adipose tissue (EAT). Furthermore, BT replacement remarkably attenuated TM-induced unfolded protein responses (UPRs) in liver, showing reduced ER stress, with BT2 being more effective in the EAT. Therefore, our findings suggest that partially replacing dietary fats with n-3 PUFA to lower the ratio of n-6/n-3 PUFAs is beneficial in preventing pathological features of MetS by alleviating HFCD- and/or TM-induced dyslipidemia and ER stress.

Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL.

Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-aged women need to be determined. The current study was designed to compare the changes in HDL quantity and quality among middle-aged women depending on exercise intensity, frequency, and duration; participants were divided into a sedentary group (group 1), a middle-intensity group (group 2), and a high-intensity group (group 3). There were no differences in anthropometric parameters among the groups, including blood pressure, muscle mass, and handgrip strength. Although there was no difference in serum total cholesterol (TC) among the groups, the serum HDL-C and apolipoprotein (apo)A-I levels remarkably increased to 17% and 12%, respectively, in group 3. Serum low-density lipoprotein-cholesterol (LDL-C), glucose, triglyceride, and the apo-B/apoA-I ratio were remarkably decreased in the exercise groups depending on the exercise intensity; group 3 showed 13%, 10%, and 45% lower LDL-C, glucose, and triglyceride (TG), respectively, than group 1. The hepatic and muscle damage parameter, aspartate aminotransferase (AST), was significantly decreased in the exercise groups, but high-sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) were similar in the three groups. In LDL, the particle size was increased 1.5-fold (p &lt; 0.001), and the oxidation extent was decreased by 40% with a 23% lower TG content in group 3 than in group 1. In the exercise groups (groups 2 and 3), LDL showed the slowest electromobility with a distinct band intensity compared to the sedentary group (group 1). In HDL2, the particle size was 2.1-fold increased (p &lt; 0.001) in the exercise group (group 3) with a 1.5-fold increase in TC content compared to that in group 1, as well as significantly enhanced antioxidant abilities, paraoxonase (PON) activity, and ferric ion reduction ability (FRA). In HDL3, the particle size was increased 1.2-fold with a 45% reduction in TG in group 3 compared to group 1. With increasing exercise intensity, apoA-I expression was increased in HDL2 and HDL3, and PON activity and FRA were enhanced (p &lt; 0.001). In conclusion, regular exercise in middle-aged women is associated with the elevation of serum HDL-C and apoA-I with the enhancement of HDL quality and functionality and an increase in the TC content, particle size, and antioxidant abilities. With the reduction in TG and oxidized products in LDL and HDL, lipoproteins could have more anti-atherogenic properties through regular exercise in an intensity-dependent manner.

Sodium Alginate Prevents Non-Alcoholic Fatty Liver Disease by Modulating the Gut-Liver Axis in High-Fat Diet-Fed Rats.

Previous studies have suggested that the sodium alginate (SA) is beneficial for the treatment of non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are largely unknown. The present study aimed to clarify the effects and potential mechanisms of SA in preventing NAFLD via the gut-liver axis. Thirty-two male Sprague-Dawley rats were randomly divided into four groups: normal control group (NC); high-fat diet group (HFD); HFD with 50 mg/kg/d sodium alginate group (LSA); HFD with 150 mg/kg/d sodium alginate group (HSA). After 16 weeks, the rats were scarified to collect blood and tissues. The results indicated that SA significantly reduced their body weight, hepatic steatosis, serum triglyceride (TG), alanine transaminase (ALT) and tumor necrosis factor α (TNF-α) levels and increased serum high-density lipoprotein-cholesterol (HDL-C) levels in comparison with HFD group (p &lt; 0.05). The elevated mRNA and protein expression of genes related to the toll-like receptor 4 (TLR-4)/nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in the liver of HFD-fed rats was notably suppressed by SA. In terms of the gut microbiota, the LSA group showed a significantly higher fecal abundance of Oscillospiraceae_UCG_005, Butyricicoccaceae_UCG_009 and Colidextribacter compared with the HFD group (p &lt; 0.05). The rats in the HSA group had a higher abundance of unclassified_Lachnospiraceae, Colidextribacter and Oscillibacter compared with the HFD-associated gut community (p &lt; 0.05). In addition, rats treated with SA showed a significant increase in fecal short chain fatty acids (SCFAs) levels and a decline in serum lipopolysaccharide (LPS) levels compared with the HFD group (p &lt; 0.05). Moreover, the modulated bacteria and microbial metabolites were notably correlated with the amelioration of NAFLD-related indices and activation of the hepatic TLR4/NF-κB/NLRP3 pathway. In conclusion, SA prevented NAFLD and the potential mechanism was related to the modulation of the gut-liver axis.

Enterococcus faecium GEFA01 alleviates hypercholesterolemia by promoting reverse cholesterol transportation via modulating the gut microbiota-SCFA axis.

This study aimed to identify cholesterol-lowering commensal strains from healthy lean individuals and to evaluate the cholesterol-lowering capacity of Enterococcus faecium GEFA01 in mice fed a high-cholesterol and high-fat diet. E. faecium GEFA01 was isolated from the feces of a healthy lean individual in a selective basal salt medium supplemented with cholesterol. E. faecium GEFA01 exhibited a cholesterol removal rate (CRR) of 46.13% by coprecipitation, assimilation, and degradation of cholesterol. Moreover, E. faecium GEFA01 significantly decreased the body weight of mice and the levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), hepatic TC, triglycerides (TG), and LDL-C, and increased serum high-density lipoprotein cholesterol (HDL-C) levels in mice fed a high-cholesterol diet compared with the HCD group. We also observed that E. faecium GEFA01 significantly downregulated the gene expression of HMG-CoA reductase (Hmgcr), Srebp-1c, Fxr, Shp, and Fgf 15, upregulated the gene expression of low-density lipoprotein receptor (Ldlr), Abcg5/8, Abca1, cholesterol 7 alpha-hydroxylase (Cyp7a1), and Lxr in the liver of mice in relative to the HCD group, markedly increased the relative abundance of Lactobacillus, Akkermansia, Bifidobacterium, and Roseburia, and decreased the abundance of Helicobacter in the feces. Collectively, we confirmed that E. faecium GEFA01 exhibited cholesterol-lowering effects in mice fed a high-cholesterol diet, which was achieved through assimilation, coprecipitation, and degradation of cholesterol, and through modulation of the gut microbiota short-chain fatty acid (SCFA) axis that promoted reverse cholesterol transport and bile acid excretion. Our study demonstrated that E. faecium GEFA01 may be used as a probiotic candidate to lower cholesterol levels in the future.

The Effects of Atorvastatin Consumption on Biochemical Variables in Patients with Type 2 Diabetes Mellitus and Pre-diabetes

Background and Aims: Atorvastatin may alter glycemic traits and lipid profiles. This study aimed to evaluate the effects of atorvastatin on biochemical variables in patients with type 2 diabetes and pre-diabetes (borderline diabetes).&#x0D; Materials and Methods: This study included 80 individuals divided into five groups. Patients with type 2 diabetes mellitus and pre-diabetes used atorvastatin 20 mg/day for three months. After three months, variables such as serum fasting blood glucose (FBS), cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and glycosylated hemoglobin (HbA1c) levels were measured to assess the status of diabetes and pre-diabetes condition. Linear regression was applied to determine the association between atorvastatin uses and alters of biochemical variables levels.&#x0D; Results: The serum FBS and HbA1c levels in patients with diabetes and pre-diabetes who use atorvastatin were significantly lower than in patients with diabetes and pre-diabetes who did not use atorvastatin (p=0.001). Serum cholesterol and LDL-C levels decreased in diabetic and pre-diabetic patients who used atorvastatin in comparison with diabetic and pre-diabetic patients who did not use atorvastatin (p=0.001). In patients with pre-diabetes, the use of atorvastatin slightly increased serum HDL-C levels. However, in patients with diabetes, the use of atorvastatin slightly decreased serum HDL-C level (p= 0.001). Diabetic and pre-diabetic patients who use atorvastatin significantly decreased serum triglyceride levels (p=0.016), while in diabetic and pre-diabetic patients, using atorvastatin slightly increased the serum insulin level (p= 0.003).&#x0D; Conclusions: Atorvastatin using alters fat and sugar indices in diabetic and pre-diabetic patients.

Effects of BBR on growth performance, serum and hepatic biochemistry parameters, hepatic morphology and gene expression levels related to glucose metabolism in largemouth bass, Micropterus salmoides

An 8-week experiment was performed to investigate the effects of BBR on growth performance, hepatic glucose metabolism, antioxidant capacity, liver histology and intestinal digestive enzyme activity of largemouth bass. Fish (initial weight ≈122 g) were randomly allocated into 16 cages (280 L, 30 fish per tank) and fed four isonitrogenous and isolipidic diets containing 0, 0.5, 1 and 2 g/kg BBR respectively. The results indicated that diets with 1 and 2 g/kg BBR significantly promoted growth, decreased serum glucose, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol but increased serum high-density lipoprotein cholesterol (p < 0.05). The application of BBR significantly decreased hepatic alanine aminotransferase, TG and TC but increased hepatic superoxide dismutase and catalase (p < 0.05). Diets with 1 and 2 g/kg BBR significantly decreased hepatic malondialdehyde, aspartate aminotransferase and hepatic glycogen but increased intestinal farnesoid X receptor and fibroblast growth factor-19 expression and dramatically altered its downstream glycolysis- and gluconeogenesis-related genes, along with their enzyme activities (p < 0.05). Supplementation with BBR increased (p < 0.05) intestinal protease activity in B5, B10 and B20, lipase activity in B10 and B20 and amylase activity in B20. BBR reduced the liver voiding rate and fat content. These results indicated that dietary supplementation with BBR at 1 and 2 g/kg was beneficial for promoting growth and health in largemouth bass. The improved glycolysis and inhibited gluconeogenesis may account for the reduced hyperglycaemia by BBR. In addition, enhancing the activity of intestinal digestive enzymes is an effective way for BBR to improve carbohydrate utilization in largemouth bass.

Polygonatum sibiricum polysaccharides protect against obesity and non-alcoholic fatty liver disease in rats fed a high-fat diet

Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance (IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease (NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides (PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.

Effect of Brain-Cor Injection of Ginkgo on the Hyperlipemia and Thrombosis: Fundamental Study

We have done this study to verify effects on the serum lipid content (TC, TG, HDL-C) in experimental model of hyperlipemia and on the blood coagulability in experimental model of thrombosis. Background: Female hormone preparation is limited in long term use because of hyperlipemia and thrombosis that are complications occurring in long term use of female hormone preparations for dysfunctional uterine bleeding, climacteric disorder, female genital organs tumor. Therefore to prevent complications such as hyperlipemia and thrombosis with female hormone preparation use are the acute problems not only for the effective treatment of gynecological diseases but also for the lowering of incidence rate of hypertension, arteriosclerosis, hyperlipemia and thrombosis. We made brain-cor injection of Ginkgo for the treatment of hyperlipemia and thrombosis that are complications occurring in long term use of female hormone preparations and verified its effects on the serum lipid content in experimental model of hyperlipemia and on the blood coagulability in experimental model of thrombosis. Objects and Materials: Wistar rats with 160~180 g in body weight were used as experimental animals, brain-cor injection of Ginkgo(70mg/20mL) made from Ginkgo extract that consists of flavonoid content above 24%, total lactone content above 6% and total ginkgolic acid content below 5μg/g was used as drugs. Methods: For 15 days brain-cor injection of Ginkgo 10mg/kg was injected in abdominal cavity of experimental model of hyperlipemia by tween-80, serum was separated from collected blood in orvita vein, serum TC (Total Cholesterol) content, serum TG (Triglyceride) content and serum HDL-C (High Density Lipoprotein-Cholesterol) content were examined with blood automatic biochemical analyzer and measurements were compared each other. For 15 days brain-cor injection of Ginkgo 10mg/kg was injected in abdominal cavity of experimental model of hyperlipemia and thromboplastin 0.5% 0.1mL/10g was injected on cauda vein in an hour after the last injection of Ginkgo. BT (Bleeding Time), CT (Clotting Time), APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time) were examined and measurements were compared each other. Results: Brain-cor injection of Ginkgo decreased serum TC and TG content and increased serum HDL-C content in experimental model of hyperlipemia. And brain-cor injection of Ginkgo prolonged BT, CT, APTT and PT significantly in experimental model of thrombosis.

Kun-Dan Decoction Ameliorates Insulin Resistance by Activating AMPK/mTOR-Mediated Autophagy in High-Fat Diet-Fed Rats.

Background: Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome. Methods: Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells. Results: Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells. Conclusion: The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.

Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism.

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.

Canagliflozin Facilitates Reverse Cholesterol Transport Through Activation of AMPK/ABC Transporter Pathway.

Background and PurposeCholesterol is an essential lipid and its homeostasis is a major factor for many diseases, such as hyperlipidemia, atherosclerosis, diabetes, and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Cana) is a new kind of hypoglycemic agent, which decreases urinary glucose reabsorption and reduces hyperglycemia. Cana has been shown to regulate serum lipid, decrease serum triglyceride and increase serum high-density lipoprotein-cholesterol (HDL-C), and improve cardiovascular outcomes. But evidence of how Cana impacted the cholesterol metabolism remains elusive.MethodsWe treated Cana on mice with chow diet or western diet and then detected cholesterol metabolism in the liver and intestine. To explore the mechanism, we also treated hepG2 cells and Caco2 cells with different concentrations of Cana.ResultsIn this study, we showed that Cana facilitated hepatic and intestinal cholesterol efflux. Mechanically, Cana via activating adenosine monophosphate-activated protein kinase (AMPK) increased the expression of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in liver and intestine, increased biliary and fecal cholesterol excretion.ConclusionThis research confirms that Cana regulates cholesterol efflux and improves blood and hepatic lipid; this may be a partial reason for improving cardiovascular disease.

88116 Effect of conjugated estrogens and bazedoxifene on glucose, energy and lipid metabolism in obese postmenopausal women

ABSTRACT IMPACT: A short treatment of 8 obese postmenopausal women with conjugated estrogens and bazedoxifene does not alter insulin sensitivity or ectopic fat but increases serum markers of hepatic de novo lipogenesis and production of triacylglycerides. OBJECTIVES/GOALS: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally-administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. METHODS/STUDY POPULATION: We conducted a randomized, double-blind, crossover pilot trial, testing the effect of CE/BZA on cardiometabolic health in postmenopausal women. Eight postmenopausal women (age 50-60 y, BMI 30-40 kg/m2) were randomization to an 8-week CE/BZA or placebo treatment separated by an 8-week washout period [NCT02274571]. The primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp), while secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); inflammatory markers; and serum metabolome (LC/MS). RESULTS/ANTICIPATED RESULTS: CE/BZA had no effect on insulin sensitivity, body composition, ectopic fat, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: p=0.06; high-dose clamp: p=0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs), and decreased long-chain acylcarnitines. These findings possibly reflect increased hepatic de novo FA synthesis and esterification into TAGs, and decreased FA oxidation, respectively (p&lt;0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in lipoproteins (p&lt;0.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: A short treatment of postmenopausal women with CE/BZA did not alter insulin action or ectopic fat, but increased markers of hepatic de novo lipogenesis and TAG production. Study limitations include a small sample size and short treatment period. A larger, fully powered study is needed to validate the potential metabolic benefit of combining CE with BZA.

Effect of dietary methionine on growth performance, lipid metabolism and antioxidant capacity of large yellow croaker (Larimichthys crocea) fed with high lipid diets

A 10-week feeding trial was conducted to evaluate the effect of dietary methionine (MET) on the growth performance, lipid metabolism and liver antioxidant function in juvenile large yellow croaker (Larimichthys crocea) fed with high lipid diets (HLDs). Large yellow croaker with an initial average weight of 8.59 g, were fed with basic HLD (lipid level at 18%, HL), basic HLD supplemented with 0.6% MET (HL/L-MET) and basic HLD supplemented with 1.2% MET (HL/H-MET). Results indicated that dietary MET did not affect weight gain, specific growth rate and feed efficiency ratio (P > 0.05). The MET supplementation in large yellow croaker also did not affect the content of total lipid in whole body (HL = 9.57, HL/L-MET = 8.92 and HL/H-MET = 8.71%), liver (7.34, 16.68 and 14.37%) and muscle (10.87, 12.11 and 9.94%) (P > 0.05). However, MET supplementation reduced the size and number of liver lipid droplets as dietary MET increased. Meanwhile, supplementation of MET in HLDs reduced serum total cholesterol (2.65, 2.14 and 1.91 mmol/L), low-density lipoprotein-cholesterol (0.27, 0.21 and 0.16 mmol/L) and triglyceride (4.80, 2.43 and 1.96 mmol/L) (P < 0.05), but increased serum high-density lipoprotein-cholesterol (0.68, 0.77 and 0.83 mmol/L) (P < 0.05). Dietary MET upregulated significantly the mRNA expression of genes related to mitochondrial fatty acid β-oxidation (PPARα and CPT1) and ER stress (GRP78, ATF6α and CHOP) (P < 0.05). Furthermore, feeding fish with MET diets reduced serum alanine transaminase and aspartate transaminase activities, serum and liver malondialdehyde content, and liver 8-hydroxydeoxyguanosine level. Interestingly, feeding fish with MET diets increased liver total antioxidant capacity activity (P < 0.05). In conclusion, dietary MET improved lipid metabolism and increased antioxidant capacity in the liver, but did not affect growth performance in juvenile large yellow croaker fed with HLDs.

Comparison of the antioxidant activities of nonfumigated and sulphur-fumigated Chrysanthemum morifolium cv. Hang-ju induced by oxidative stress

Context The traditional drying method, sun drying, for Chrysanthemum morifolium Ramat. cv. Hang-ju (Compositae) (HJ) is widely replaced by sulphur fumigation (SF), which has an unknown effect on its efficacy. Objective To investigate protective effects of nonfumigated HJ (NHJ) and sulphur-fumigated HJ (SHJ) water extracts against oxidative stress and lipid peroxidation. Materials and methods Sprague-Dawley rats were administered high-fat diet to induce hyperlipidaemia and randomly divided into eight groups (n = 6): control, fenofibrate, NHJ and SHJ extracts (1, 2 or 4 g crude drugs/kg/d; intragastric administration for 8 weeks). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Human umbilical vein endothelial cells (HUVECs) were treated with NHJ and SHJ extracts (50, 100 or 200 μg/mL) for 24 h, followed by oxidized low-density lipoprotein (ox-LDL, 20 μg/mL) for 2 h in vitro. Cellular reactive oxygen species (ROS), SOD and MDA levels and apoptosis were evaluated. Results NHJ was more effective than SHJ in decreasing serum TG, TC, LDL-C, LDL/HDL and MDA while increasing serum HDL-C and SOD levels at high doses. SHJ (IC50=19.9 mg/mL) suppressed HUVEC growth stronger than NHJ (IC50=186.7 mg/mL). At 200 μg/mL, NHJ was more effective than SHJ in downregulating ROS and MDA levels, reducing HUVECs apoptosis rate and elevating SOD activity in ox-LDL-treated HUVECs. Conclusions SF causes oxidative damage and attenuates antioxidative activity in ox-LDL-treated HUVECs, which promotes lipid peroxidation. SF is not recommended for processing HJ.

The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High‐Fat Diet‐Fed Mice

The marine horseshoe crab (Tachypleus tridentatus) has been considered as food and traditional medicine for many years. Kynurenic acid (KA) was isolated from horseshoe crab in this study for the first time in the world. A previous study in 2018 reported that intraperitoneal administration of KA prevented high-fat diet- (HFD-) induced body weight gain. Now, we investigated the effects of intragastric gavage of KA on HFD mice and found that KA (5 mg/kg/day) inhibited both the body weight gain and the increase of average daily energy intake. KA reduced serum triglyceride and increased serum high-density lipoprotein cholesterol. KA inhibited HFD-induced the increases of serum low-density lipoprotein cholesterol, coronary artery risk index, and atherosclerosis index. KA also suppressed HFD-induced the increase of the ratio of Firmicutes to Bacteroidetes (two dominant gut microbial phyla). KA partially reversed HFD-induced the changes in the composition of gut microbial genera. These overall effects of KA on HFD mice were similar to that of simvastatin (positive control). But the effects of 1.25 mg/kg/day KA on HFD-caused hyperlipidemia were similar to the effects of 5 mg/kg/day simvastatin. The pattern of relative abundance in 40 key genera of gut microbiota from KA group was closer to that from the normal group than that from the simvastatin group. In addition, our in vitro results showed the potential antioxidant activity of KA, which suggests that the improvement effects of KA on HFD mice may be partially associated with antioxidant activity of KA. Our findings demonstrate the potential role of KA as a functional food ingredient for the treatment of obesity and hyperlipidemia as well as the modulation of gut microbiota.

Abstract 16851: Lipid Profile Differences Among Premenopausal and Postmenopausal African American Women and Implications for Treatment Per Guideline

Introduction: Postmenopausal women have an increased cardiovascular disease (CVD) risk compared to premenopausal women. Though literature demonstrates a relationship between abnormal CVD risk factor patterns, namely lipids, and menopause, less is known about this association in minority racial and ethnic groups. Examining this association in African Americans (AA) is important because they experience disproportionate CVD outcomes. Moreover, recent studies have shown that AA eligible for statin therapy were less likely to receive treatment. Hypothesis: Postmenopausal women are more likely to have a more abnormal lipid profile compared to premenopausal women. Methods: A cohort of 962 women (mean age 50 ± 14 years) from the 10,000 Women Project were categorized into self-declared premenopausal (n = 475, mean age 40 ± 9.8 years) and postmenopausal (n= 487, mean age 61 ± 9.1 years) groups. Data was obtained at community health screening events through self-declared health history surveys. Lipid profiles were obtained through a non-fasting point-of-care cholesterol test. Several CVD risk factors were compared among these groups that include serum total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG), pooled cohort Atherosclerotic Cardiovascular Disease (ASCVD) 10-year risk of heart disease or stroke score, BMI, waist circumference, and blood pressure. Student’s T test was utilized for statistical analysis. Results: Cholesterol testing revealed a significant increase in serum TC (p &lt; 0.0001), LDL (p = 0.0001), and TG (p = 0.001) in the postmenopausal group compared to the premenopausal group. Interestingly, there was also a significant increase in serum HDL in the postmenopausal group (p = 0.0081). Additionally, the ASCVD risk score, which is heavily weighted on age, was significantly higher in the postmenopausal group compared to the premenopausal group (p &lt; 0.0001). Conclusion: Menopause is associated with a more abnormal lipid profile and an elevated ASCVD risk score in AA women which places this group at a higher risk of CVD. Prioritizing lipid management, by adhering to cholesterol treatment guidelines, may assist with CVD risk reduction in this high-risk group.

A high-fat diet and high-fat and high-cholesterol diet may affect glucose and lipid metabolism differentially through gut microbiota in mice.

This study was conducted to investigate the effects of a high-fat diet (HFD) and high-fat and high-cholesterol diet (HFHCD) on glucose and lipid metabolism and on the intestinal microbiota of the host animal. A total of 30 four-week-old female C57BL/6 mice were randomly divided into three groups (n=10) and fed with a normal diet (ND), HFD, or HFHCD for 12 weeks, respectively. The HFD significantly increased body weight and visceral adipose accumulation and partly lowered oral glucose tolerance compared with the ND and HFHCD. The HFHCD increased liver weight, liver fat infiltration, liver triglycerides, and liver total cholesterol compared with the ND and HFD. Moreover, it increased serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol compared with the ND and HFD and upregulated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase significantly. The HFHCD also significantly decreased the α-diversity of the fecal bacteria of the mice, to a greater extent than the HFD. The composition of fecal bacteria among the three groups was apparently different. Compared with the HFHCD-fed mice, the HFD-fed mice had more Oscillospira, Odoribacter, Bacteroides, and [Prevotella], but less [Ruminococcus] and Akkermansia. Cecal short-chain fatty acids were significantly decreased after the mice were fed the HFD or HFHCD for 12 weeks. Our findings indicate that an HFD and HFHCD can alter the glucose and lipid metabolism of the host animal differentially; modifications of intestinal microbiota and their metabolites may be an important underlying mechanism.