Effects of Free Linoleic Acid and Oleic Acid in Sesame Meal Extract as Pancreatic Lipase Inhibitors on Postprandial Triglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Volunteers.

A great number of chemically diverse pancreatic lipase (PL) inhibitors have been identified to tackle obesity; however, very few of them have entered clinical studies. The ethanolic extract of sesame meal is a potent PL inhibitor, and its activity hinges exclusively on two free fatty acids: linoleic acid and oleic acid, which were proven to reduce postprandial triglyceride excursion in rats. Herein, to investigate the clinical efficacy of the sesame meal extract, in a crossover trial, 30 healthy volunteers were randomized to receive the sesame meal extract containing experimental food or placebo along with a high-fat meal. Treatment with the sesame meal extract significantly lowered the incremental postprandial serum triglyceride concentration and reduced the incremental area under the curve (iAUC) by 16.8% (p-value = 0.03) compared to placebo. Significant decreases in postprandial remnant-like lipoprotein particle cholesterol and low-density lipoprotein particles were also observed, whereas high-density lipoprotein cholesterol was increased. These results suggest that treatment with the sesame meal extract significantly reduced the postprandial excursion of triglycerides and improved the lipidemic profile after high dietary fat intake in healthy individuals, indicating the substantial potential of free linoleic acid and oleic acid and natural products rich in these compounds for the management of obesity and related conditions.

Oral fat tolerance testing identifies abnormal pancreatic ß-cell function and insulin resistance in individuals with normal glucose tolerance.

AIMS/INTRODUCTION: Insulin sensitivity and ß-cell function are affected by lipid metabolism disorders, even before the onset of type 2 diabetes. People are in the postprandial state most of the time. Therefore, identifying postprandial hyperlipemia is important. This study aimed to assess patients with abnormalities in lipid metabolism, but with normal glucose tolerance, using oral fat tolerance testing (OFTT) to identify defects in insulin sensitivity and ß-cell function. MATERIALS AND METHODS: We included 248 volunteers with normal glucose tolerance who underwent OFTT. They were divided into three groups in accordance with their fasting and 4-h postprandial triglyceride (TG) concentrations. Their lipid concentrations during OFTT were compared. The disposition index (DI) was applied to estimate ß-cell function, and the Matsuda insulin sensitivity index (ISIM ) was used to assess insulin sensitivity. We used multiple linear regression analysis to estimate the relationships of fasting and postprandial TG concentrations with ß-cell function and insulin sensitivity . RESULTS: The changes in TG concentrations during OFTT were more marked than those in low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol or total cholesterol concentrations. As lipid metabolism deteriorated, the ISIM and the DI gradually decreased. Multiple linear regression analysis showed that fasting and 4-h postprandial TG concentrations affected LnISIM and LnDI. CONCLUSIONS: In individuals with normal glucose tolerance, ß-cell function and insulin sensitivity gradually decrease with a deterioration in the lipid profile. Not only fasting TG, but also postprandial TG concentrations are independent risk factors for impaired ß-cell function and insulin resistance.

Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test.

The use of meal challenge tests to assess postprandial responses in carbohydrate and fat metabolism is well established in clinical nutrition research. However, challenge meal compositions and protocols remain a variable. Here, we validated a mixed macronutrient tolerance test (MMTT), containing 56-g palm oil, 59-g sucrose, and 26-g egg white protein for the parallel determination of insulin sensitivity and postprandial triglyceridemia in clinically healthy subjects. The MMTT was administered in two study populations. In one, women with overweight/obese BMIs (n = 43) involved in an 8-week dietary intervention were administered oral glucose tolerance tests (OGTTs) and MMTTs within 2 days of each other after 0, 2, and 8 weeks of the dietary intervention. In the other, 340 men and women between 18 and 64 years of age, with BMI from 18-40 kg/m2, completed the MMTT as part of a broad nutritional phenotyping effort. Postprandial blood collected at 0, 0.5, 3, and 6 h was used to measure glucose, insulin, and clinical lipid panels. The MMTT postprandial insulin-dependent glucose disposal was evaluated by using the Matsuda Index algorithm and the 0- and 3 h blood insulin and glucose measures. The resulting MMTT insulin sensitivity index (ISIMMTT) was strongly correlated (r = 0.77, p < 0.001) with the OGTT-dependent 2 h composite Matsuda index (ISIComposite), being related by the following equation: Log (ISIComposite) = [0.8751 x Log(ISIMMTT)] -0.2115. An area under the triglyceride excursion curve >11.15 mg/mL h-1 calculated from the 0, 3, and 6 h blood draws established mild-to-moderate triglyceridemia in agreement with ∼20% greater prevalence of hypertriglyceridemia than fasting indications. We also demonstrated that the product of the 0 to 3 h and 3 to 6 h triglyceride rate of change as a function of the triglyceride incremental area under the curve optimally stratified subjects by postprandial response patterns. Notably, ∼2% of the population showed minimal triglyceride appearance by 6 h, while ∼25% had increasing triglycerides through 6 h. Ultimately, using three blood draws, the MMTT allowed for the simultaneous determination of insulin sensitivity and postprandial triglyceridemia in individuals without clinically diagnosed disease. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT02298725; NCT02367287].

The 494th case: acute pancreatitis, acute acalculous cholecystitis and anaphylaxis / 中华内科杂志

A young male patient with abdominal pain and fever was diagnosed as acute hyper-triglyceridemicpancreatitis is clear. During the recovery of pancreatitis, the patient developed acute acalculous cholecystitis, as well as carbapenem-resistant Enterobacter infection and Cytomegaloviremia, and had anaphylaxis for several times after the use of antibiotics, which cannot be completely explained by drug allergy. This paper analyzes the possible causes of multiple diseases in the same patient in detail.

Associations of serum transthyretin with triglyceride in non-obese elderly Japanese women independently of insulin resistance, HDL cholesterol, and adiponectin.

OBJECTIVE: Studies are limited on the association between serum transthyretin (TTR), a negative acute phase reactant, and triglyceride (TG). RESEARCH DESIGN AND METHODS: TG, TTR, and insulin resistance-related cardiometabolic variables were measured in 159 fasting and 185 nonfasting community-dwelling elderly women aged 50-96 years. Pearson correlation analysis and then stepwise multiple regression analyses were performed to further identify the most significant variables contributing to the variation of fasting and nonfasting TG. RESULTS: Multiple regression analysis for fasting TG as a dependent variable revealed that TTR (standardized ß: 0.299) and HDL cholesterol (standardized ß: -0.545) emerged as determinants of TG independently of percentage of body fat, homeostasis model assessment insulin resistance, serum leptin and adiponectin, and plasminogen activator inhibitor-1 (PAI-1) (R 2 = 0.36). For nonfasting TG, HDL cholesterol (standardized ß: - 0.461), TTR (standardized ß: 0.231), nonfasting insulin, a marker of insulin resistance, (standardized ß: 0.202), and PAI-1 (standardized ß: 0.187) emerged as determinants independently of percentage of body fat, nonfasting glucose, serum leptin and adiponectin, and high-sensitivity C-reactive protein (R 2 = 0.45). CONCLUSIONS: Fasting and nonfasting TG showed positive association with TTR in community-dwelling elderly non-obese women independently of insulin resistance, HDL cholesterol, and adiponectin. These findings may provide a clue as to a physiological function of circulating TTR in human: an influence factor of TG-rich lipoproteins in the circulation.

The Influence of Different Foods and Food Ingredients on Acute Postprandial Triglyceride Response: A Systematic Literature Review and Meta-Analysis of Randomized Controlled Trials.

The use of postprandial triglyceride (ppTG) as a cardiovascular disease risk indicator has gained recent popularity. However, the influence of different foods or food ingredients on the ppTG response has not been comprehensively characterized. A systematic literature review and meta-analysis was conducted to assess the effects of foods or food ingredients on the ppTG response. PubMed, MEDLINE, Cochrane, and CINAHL databases were searched for relevant acute (<24-h) randomized controlled trials published up to September 2018. Based on our selection criteria, 179 relevant trials (366 comparisons) were identified and systematically compiled into distinct food or food ingredient categories. A ppTG-lowering effect was noted for soluble fiber (Hedges' giAUC = -0.72; 95% CI: -1.33, -0.11), sodium bicarbonate mineral water (Hedges' gAUC = -0.42; 95% CI: -0.79, -0.04), diacylglycerol oil (Hedges' giAUC = -0.38; 95% CI: -0.75, -0.00), and whey protein when it was contrasted with other proteins. The fats group showed significant but opposite effects depending on the outcome measure used (Hedges' giAUC = -0.32; 95% CI: -0.61, -0.03; and Hedges' gAUC = 0.16; 95% CI: 0.06, 0.26). Data for other important food groups (nuts, vegetables, and polyphenols) were also assessed but of limited availability. Assessing for oral fat tolerance test (OFTT) recommendation compliance, most trials were ≥4 h long but lacked a sufficiently high fat challenge. iAUC and AUC were more common measures of ppTG. Overall, our analyses indicate that the effects on ppTG by different food groups are diverse, largely influenced by the type of food or food ingredient within the same group. The type of ppTG measurement can also influence the response.

Discrepancy Between Fasting Flow-Mediated Dilation and Parameter of Lipids in Blood: A Randomized Exploratory Study of the Effect of Omega-3 Fatty Acid Ethyl Esters on Vascular Endothelial Function in Patients With Hyperlipidemia.

INTRODUCTION: Omega-3 fatty acid ethyl esters (omega-3), an eicosapentaenoic acid and docosahexaenoic acid preparation (Lotriga®, Takeda Pharmaceutical Company Limited), are approved in Japan to treat triglyceridemia. We investigated the effects of omega-3 on vascular endothelial function, measured by flow-mediated dilation (FMD). METHODS: Patients with dyslipidemia receiving 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors were randomized 1:1 to receive omega-3 at 2 g (QD) or 4 g (2 g BID) for 8 weeks. The primary end point was the change from baseline of fasting  %FMD in each treatment group. Secondary end points included the 4-h postprandial  %FMD and 4-h postprandial triglyceride (TG) level. RESULTS: Thirty-seven patients were randomized to receive omega-3 at 2 g (n = 18) or 4 g (n = 19). Mean fasting %FMD did not increase from baseline to week 8 in the 2-g group (- 1.2%) or 4-g group (- 1.3%). Mean 4-h postprandial %FMD did not change from baseline to week 8 in the 2-g group (0.0%), but increased in the 4-g group (1.0%). Mean 4-h postprandial TG level decreased by 34.7 mg/dl from baseline over week 8 in the 2-g group, with a significantly larger decrease in the 4-g group of 75.9 mg/dl (p < 0.001). No new safety concerns were identified. CONCLUSIONS: Fasting %FMD did not improve after 8 weeks of omega-3 treatment at 2 g or 4 g. After 8 weeks, 4-h postprandial TG levels showed improvement at both doses, with a greater reduction in the 4-g group. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02824432.

ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population.

BACKGROUND: The ABCG2 rs2231142 single nucleotide polymorphism (SNP) is one of the most significant genetic variants associated with hyperuricemia (HUA) in Asian populations. However, the risk of ABCG2 rs2231142 variants for HUA could interact with other important HUA risk variants and cardiovascular factors. This study investigated the effects of the combined association among ABCG2 rs2231142 and multiple HUA genetic variants or cardiovascular risk factors on HUA risk and serum uric acid (sUA) levels in an elderly Chinese population. METHODS: A total of 1206 participants over 65 years old were enrolled in this study. Physical and laboratory examinations were performed for all participants. The ABCG2 rs2231142, SLC2A9 rs3733591, and SLC22A12 rs893006 SNPs were assayed using a standardized protocol. Logistic regression analysis and liner regression were adjusted respectively to account for the association between ABCG2 rs2231142 and other genetic variants, as well as between cardiovascular risk factors and HUA risk and sUA levels. RESULTS: The prevalence of HUA was 14.71% in the elderly community-dwelling population. The ABCG2 rs2231142 risk T allele was associated with HUA risk (odds ratio (OR) = 1.63, 95% confidence interval (CI): 1.27-2.11; p = 1.65 × 10- 4) and with increased sUA levels (Beta = 0.16, p = 6.75 × 10- 9) in the whole study population. Linear regression analysis showed that the mean sUA level increased linearly with the number of risk alleles of the three candidate genetic variants (Beta = 0.18, p = 1.94 × 10- 12) The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased HUA risk and sUA levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia (OR = 2.52, 95% CI: 1.33-4.60; p = 0.003) compared to controls. CONCLUSION: Our findings reinforce the importance of the ABCG2 rs2231143 variant as a crucial genetic locus for HUA in Chinese populations and demonstrated the combined effects of multiple genetic risk variants and cardiovascular risk exposures on HUA risk and increased sUA level.

Intervention of Ayurvedic drug Tinospora cordifolia attenuates the metabolic alterations in hypertriglyceridemia: a pilot clinical trial.

PURPOSE: Hypertriglyceridemia (HG) is an independent risk factor with more prevalence than hypercholesterolemia and its attributes to cardiovascular disease (CVD) and pancreatitis. Hence, it becomes imperative to search for new triglyceride (TG) lowering agents. Tinospora cordifolia (TC) is a well-known Ayurvedic drug and a rich source of protoberberine alkaloids hence can contribute to TG lowering without side effects. Hence, to explore the therapeutic efficacy of T. cordifolia and its effects on biochemistry and metabolome in the patients of hyper-triglyceridemia, clinical trials were conducted. METHODS: Patients (n = 24) with hypertriglyceridemia were randomized into two groups to receive T. cordifolia extract (TCE) (3.0 g/per day) and metformin (850 mg/day) for 14 days having >300 mg/dl triglyceride level and cholesterol in the range of 130-230 mg/dl. Lipid profiles of blood samples were analyzed. Urine samples were subjected to HPLC-QTOF-MS to quantify oxidative damage and abnormal metabolic regulation. RESULTS: Intervention with TCE reduced the triglyceride, LDL, and VLDL levels to 380.45 ± 17.44, 133.25 ± 3.18, and 31.85 ± 5.88 mg/dL and increased the HDL to 47.50 ± 9.05 mg/dL significantly (p < 0.05) in the HG patients after 14 days treatment. TCE dosage potently suppressed the inflammatory and oxidative stress marker's i.e. levels of isoprostanes significantly (p < 0.01). Qualitative metabolomics approach i.e. PCA and PLS-DA showed significant alterations (p < 0.05) in the levels of 40 metabolites in the urine samples from different groups. CONCLUSION: TCE administration depleted the levels of markers of HG i.e. VLDL, TG, and LDL significantly. Metabolomics studies established that the anti-HG activity of TCE was due to its antioxidative potential and modulation of the biopterin, butanoate, amino acid, and vitamin metabolism. CLINICAL TRIALS REGISTRY: India (CTRI) registration no. CTRI- 2016-08-007187.

Polyphenol-rich curry made with mixed spices and vegetables benefits glucose homeostasis in Chinese males (Polyspice Study): a dose-response randomized controlled crossover trial.

PURPOSE: To investigate acute effects of two doses of a polyphenol-rich curry made with seven different spices and four base vegetables, eaten with white rice, on 24 h glucose response, postprandial insulinemia, triglyceridemia and 24 h urinary total polyphenol excretion (TPE). METHODS: Randomized, controlled, dose-response crossover trial in healthy, Chinese men [n = 20, mean ± standard deviation (SD) age 23.7 ± 2.30 years, BMI 23.0 ± 2.31 kg/m2] who consumed test meals matched for calories, macronutrients and total vegetables content, consisting either Dose 0 Control (D0C) or Dose 1 Curry (D1C) or Dose 2 Curry (D2C) meal. 24 h glucose concentration was measured using continuous glucose monitoring (CGM), together with postprandial plasma insulin and triglyceride for up to 7 h. Total polyphenol content (TPC) of test meals and urinary TPE were measured using the Folin-Ciocalteu assay. RESULTS: TPC for D0C, D1C and D2C were 130 ± 18, 556 ± 19.7 and 1113 ± 211.6 mg gallic acid equivalent (GAE) per portion served, respectively (p < 0.0001). Compared with D0C meal, we found significant linear dose-response reductions in the 3-h postprandial incremental AUC (iAUC) for CGM glucose of 19% and 32% during D1C and D2C meals respectively (p < 0.05) and non-significant linear dose response reductions in iAUC of insulin (p = 0.089). Notably, we found significant dose-dependent increases in postprandial triglyceride with increasing curry doses (p < 0.01). Significant increases in TPE with increasing curry doses were also observed (p < 0.01). CONCLUSION: Polyphenol-rich curry intake can improve postprandial glucose homeostasis. The longer term effects remain to be established.

Effects of Fiber Purified Extract of Carob Fruit on Fat Digestion and Postprandial Lipemia in Healthy Rats.

Increased postprandial lipemia is a cardiovascular disease (CVD) risk factor. Carob fruit extract (CFE) contains condensed tannins, and their intake has been inversely related to CVD. The objective was to evaluate the in vitro pancreatic lipase activity in the presence of CFE and the in vivo effect of CFE on postprandial lipemia of healthy Wistar rats in acute and subchronic digestibility studies and to relate it with changes in fat digestion and absorption. CFE significantly reduced pancreatic lipase activity. A peak delay and a dose-dependent decrease in plasma triglyceride and cholesterol areas under the curve were observed, effects that increased after the subchronic treatment. The levels of nondigested, nonabsorbed triglycerides of the remaining intestinal lumen fat were significantly higher in the maximum dose of CFE administrated versus the control ( P < 0.05). This study demonstrates for the first time the hypolipemic properties of CFE from the first administration, modifying postprandial lipemia by reducing the extents of fat digestion and absorption.

Hypertriglyceridemia in female rats during pregnancy induces obesity in male offspring via altering hypothalamic leptin signaling.

Maternal obesity influence the child's long-term development and health. Though, the mechanism concerned in this process is still uncertain. In the present study, we explored whether overfeeding of a high-fat diet during pregnancy in female rats altered metabolic phenotypes in an F1 generation and authenticated the contribution of hypothalamic leptin signaling. Leptin responsiveness and the number of immunopositive neurons for phosphorylated signal transducer and activator transcription 3 (pSTAT3) were analyzed. Neuropeptide Y in the arcuate nucleus of the hypothalamus and in nucleus tractus solitaries was examined. Triglycerides and leptin levels were increased in the high-fat diet mother. The number of neuropeptide Y positive cell bodies and neurons was significantly increased in the high-fat diet-F1 offspring (HDF-F1) as compared to Chow-F1. Leptin administration significantly decreased the food intake and increased the pSTAT3 expression levels in neurons in the arcuate nucleus of Chow-F1. However, leptin did not show any effect on food intake and had a reduced effect on pSTAT3 expression levels in neurons in the arcuate nucleus of HDF-F1. From the present domino effect, we conclude that mothers exposed to high-fat diet during pregnancy may pass the obese phenotype to the succeeding generation via altering hypothalamic leptin signaling.

Postprandial lipemia: factoring in lipemic response for ranking foods for their healthiness.

One of the limitations for ranking foods and meals for healthiness on the basis of the glycaemic index (GI) is that the GI is subject to manipulation by addition of fat. Postprandial lipemia, defined as a rise in circulating triglyceride containing lipoproteins following consumption of a meal, has been recognised as a risk factor for the development of cardiovascular disease and other chronic diseases. Many non-modifiable factors (pathological conditions, genetic background, age, sex and menopausal status) and life-style factors (physical activity, smoking, alcohol and medication use, dietary choices) may modulate postprandial lipemia. The structure and the composition of a food or a meal consumed also plays an important role in the rate of postprandial appearance and clearance of triglycerides in the blood. However, a major difficulty in grading foods, meals and diets according to their potential to elevate postprandial triglyceride levels has been the lack of a standardised marker that takes into consideration both the general characteristics of the food and the food's fat composition and quantity. The release rate of lipids from the food matrix during digestion also has an important role in determining the postprandial lipemic effects of a food product. This article reviews the factors that have been shown to influence postprandial lipemia with a view to develop a novel index for ranking foods according to their healthiness. This index should take into consideration not only the glycaemic but also lipemic responses.

Factors associated with high cardiovascular risk in a primarily African American, urban HIV-infected population.

OBJECTIVE: To determine factors associated with increased risk of developing cardiovascular disease in a high-risk patient population. DESIGN: Cross-sectional analysis of a retrospective cohort study. METHODS: One-hundred patients at an inner city HIV clinic in 2008 were reviewed. The atherosclerotic vascular disease risk score was calculated using the Pooled Cohort Equation. Chi-square test was performed to identify associations of potential risk factors with elevated atherosclerotic vascular disease risk. RESULTS: Eighty-one participants were included in the final analysis. In total, 95.1% were African American, and 38.3% were women. The median atherosclerotic vascular disease risk score was 8.8% and 8.1% in 2008 and 2012, respectively. The medical co-morbidities associated with increased atherosclerotic vascular disease risk were hepatitis C infection (X2 = 3.93; p value = 0.048), elevated triglycerides levels (X2 = 4.0; p value = 0.046), and low albumin (X2 = 4.65; p value = 0.031). There were a higher number of women with known atherosclerotic vascular disease despite lower median atherosclerotic vascular disease risk score compared to men. CONCLUSION: An elevated risk of developing cardiovascular disease persists in high-risk demographic groups of the HIV epidemic even in the current HIV era. There is an unexplained gender disparity and some non-traditional risk factors not accounted for in the Pooled Cohort Equation may be contributing to the excess cardiovascular disease risk observed among HIV-infected patients.

Severe insomnia is associated with hypertriglyceridemia in women with major depression treated in psychiatry settings.

BACKGROUND: Hypertriglyceridemia (HTG) is a cardiovascular risk factor. In the general population, elevated fasting triglyceridemia (TG) is associated with insomnia. Since insomnia is a core symptom of Major Depressive Episodes (MDE), we studied the association of severe insomnia with HTG in major depression. METHODS: We used the baseline data of the METADAP cohort, comprising 624 patients with a current MDE in a context of Major Depressive Disorder treated in psychiatry settings, without current alcohol use disorders. Patients were screened for severe insomnia, defined by a score of four or more on the three Hamilton Depression Rating Scale (HDRS) sleep items, and for HTG characterised by TG≥200mg/dL. RESULTS: Severe insomnia was observed in 335(54%) patients with a current MDE, of whom 234(70%) were women; 49(8%) patients had HTG, of whom 25(51%) were women. 69(11%) patients were treated with lipid-lowering drugs. Severe insomnia was associated with a higher frequency of HTG in the whole sample (9.9% vs 5.6%, p=0.046) and in the subgroup of women (9.0% vs 2.0%, p=0.002). Multivariate logistic regression analyses adjusted for age, education levels, BMI and total HDRS scores confirmed the association between severe insomnia and HTG in the whole sample (OR=2.02, 95%CI [1.00-4.08], p=0.05) as well as in the subgroup of women (OR=4.82, 95%CI [1.5-15.5], p=0.008). No association was shown in men. PERSPECTIVES: HTG should be systematically investigated in depressed patients with severe insomnia and particularly in women. Further studies are needed to explain the association we observed between severe insomnia and HTG.

Role of leptin in body temperature regulation and lipid metabolism following splenectomy.

OBJECTIVE: The physiological changes in serum triglycerides and body temperature that are induced by splenectomy are poorly understood. Therefore, the aim of this study was to investigate parameters related to lipid and glucose metabolism, as well as thermoregulation, in splenectomized mice. DESIGN AND METHODS: Splenectomized and sham-operated WT mice (C57Bl/6) and ob/ob mice were randomly divided and treated with a standard or high fat diet, and several metabolic parameters and the body temperature were investigated. RESULTS: Splenectomy induced a significant increase in triglyceride levels regardless of the diet. It was found that the splenectomized WT mice showed greater serum leptin and insulin levels compared with the sham-operated mice. Additionally, the body temperatures of the splenectomized WT mice were greater than the body temperatures of the control animals regardless of diet; this result too was observed without any significant change in the temperature of the splenectomized ob/ob animals. CONCLUSION: The results suggest that splenectomy interferes with serum triglyceride metabolism and body temperature regardless of the fat content in the diet and that leptin is involved in the regulation of body temperature related to splenectomy.

Beneficial effects of a flavanol-enriched cacao beverage on anthropometric and cardiometabolic risk profile in overweight subjects / Efectos beneficiosos de una bebida de cocoa enriquecida con flavanol en el perfil antropométrico y de riesgo cardiometabólico en sujetos con sobrepeso

Overweight and obesity are associated with systemic inflammation and oxidative stress which, in turn, enhance the development of cardiometabolic disruptions. Lifestyle changes and pharmacologic approaches show moderately effective results regarding overall health improvements. Evidence suggests that cacao flavonoids are associated with a reduced cardiometabolic risk, due to the modulation of molecular pathways subjacent to glucose and lipids metabolism. The aim of this study was to assess the effects of cacao flavonoids supplementation on anthropometric and cardiometabolic risk factors in overweight subjects. A double-blind, placebo-controlled, pilot clinical trial was conducted in overweight subjects with borderline criteria of metabolic syndrome. Participants were randomly assigned to either, supplement of cacao flavonoids (80 mg) or placebo, daily, for 4 weeks. Cardiometabolic variables were blood pressure, glycemia and lipid profile. Serum markers of oxidative damage (free protein carbonyls and malondialdehyde) were also analyzed. Anthropometric measurements included body weight, body mass index, waist circumference, and fat and fat-free mass. We found significant reductions in body weight (p = 0.04), waist circumference (p = 0.03), triacylglycerols (p < 0.01), TG/HDL ratio (p = 0.01), MDA (p = 0.02) and protein carbonyls (p = 0.01) in the flavonoid-supplemented group. Results from this study show that cacao flavonoids can effectively modulate anthropometric and cardiometabolic risk factors.

El sobrepeso y la obesidad están asociados con la inflamación sistémica y el estrés oxidativo, que, a su vez, incrementan el desarrollo de trastornos cardiometabólicos. Cambios en el estilo de vida y tratamientos farmacológicos muestran resultados moderadamente eficaces en relación con la mejora general de la salud. La evidencia sugiere que los flavonoides del cacao se asocian con un riesgo cardiometabólico reducido, debido a la modulación de las vías moleculares subyacentes al metabolismo de la glucosa y de los lípidos. El objetivo de este estudio fue evaluar los efectos de la suplementación de flavonoides del cacao sobre factores de riesgo cardiometabólico y antropométrico en sujetos con sobrepeso. Se llevó a cabo un ensayo clínico piloto, doble ciego y controlado con placebo en sujetos con sobrepeso y criterios limítrofes de síndrome metabólico. Los participantes fueron asignados al azar a cuatro semanas de tratamiento con suplemento oral de flavonoides de cacao (80 mg) diario o placebo. Las variables cardiometabólicas analizadas fueron presión arterial sistémica, glicemia y perfil lipídico. También se analizaron los marcadores séricos de estrés oxidativo (carbonilos proteicos libres y malondialdehído). Las medidas antropométricas incluyeron el peso corporal, índice de masa corporal, circunferencia de la cintura, masa grasa y masa libre de grasa. Se encontró una reducción significativa en el peso corporal (p = 0.04), circunferencia de la cintura (p = 0.03), triglicéridos (p < 0.01), la relación TG/HDL (p = 0.01), MDA (p = 0.02) y carbonilos (p = 0.01) en el grupo con suplemento de flavonoides. Los resultados de este estudio muestran que los flavonoides del cacao pueden modular efectivamente factores de riesgo cardiometabólico y antropométricos.

Embryonic viability, lipase deficiency, hypertriglyceridemia and neonatal lethality in a novel LMF1-deficient mouse model.

BACKGROUND: Lipase Maturation Factor 1 (LMF1) is an ER-chaperone involved in the post-translational maturation and catalytic activation of vascular lipases including lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). Mutations in LMF1 are associated with lipase deficiency and severe hypertriglyceridemia indicating the critical role of LMF1 in plasma lipid homeostasis. The currently available mouse model of LMF1 deficiency is based on a naturally occurring truncating mutation, combined lipase deficiency (cld), which may represent a hypomorphic allele. Thus, development of LMF1-null mice is needed to explore the phenotypic consequences of complete LMF1 deficiency. FINDINGS: In situ hybridization and qPCR analysis in the normal mouse embryo revealed ubiquitous and high-level LMF1 expression. To investigate if LMF1 was required for embryonic viability, a novel mouse model based on a null-allele of LMF1 was generated and characterized. LMF1-/- progeny were born at Mendelian ratios and exhibited combined lipase deficiency, hypertriglyceridemia and neonatal lethality. CONCLUSION: Our results raise the possibility of a previously unrecognized role for LMF1 in embryonic development, but indicate that LMF1 is dispensable for the viability of mouse embryo. The novel mouse model developed in this study will be useful to investigate the full phenotypic spectrum of LMF1 deficiency.

Development of novel benzomorpholine class of diacylglycerol acyltransferase I inhibitors.

Diacylglycerol acyltransferase 1 (DGAT1) presents itself as a potential therapeutic target for obesity and diabetes for its important role in triglyceride biosynthesis. Herein we report the rational design of a novel class of DGAT1 inhibitors featuring a benzomorpholine core (23n). SAR exploration yielded compounds with good potency and selectivity as well as reasonable physical and pharmacokinetic properties. This class of DGAT1 inhibitors was tested in rodent models to evaluate DGAT1 inhibition as a novel approach for the treatment of metabolic diseases. Compound 23n conferred weight loss and a reduction in liver triglycerides when dosed chronically in mice with diet-induced obesity and depleted serum triglycerides following a lipid challenge.