Fat Load Research Articles

Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored.MethodsIn the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique.ResultsThe results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load.ConclusionsThere is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.

The association of red and processed meat with gestational diabetes mellitus: Results from 2 Canadian birth cohort studies.

Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada. This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders. There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load. Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada.

Adipose Tissue Hypoxia in Obesity: Clinical Reappraisal of Hypoxia Hypothesis.

Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thereby, compared to lean subjects, obese individuals have almost half lower capillary density and more than half lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 alpha (HIF-1α) activity also requires phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR)-mediated signaling. Especially HIF-1α is an important signaling molecule for hypoxia to induce the inflammatory responses. Hypoxia contributes to several biological functions, such as angiogenesis, cell proliferation, apoptosis, inflammation, and insulin resistance (IR). Pathogenesis of obesity-related comorbidities is attributed to intermittent hypoxia (IH), which is mostly observed in visceral obesity. Proinflammatory phenotype of the adipose tissue is a crucial link between IH and the development of IR. Inhibition of adaptive unfolded protein response (UPR) in hypoxia increases β cell death. Moreover, deletion of HIF-1α worsens β cell function. Oxidative stress, as well as the release of proinflammatory cytokines/adipokines in obesity, is proportional to the severity of IH. Reactive oxygen species (ROS) generation at mitochondria is responsible for propagation of the hypoxic signal; however, mitochondrial ROS production is required for hypoxic HIF-1α protein stabilization. Alterations in oxygen availability of adipose tissue directly affect the macrophage polarization and are responsible for the dysregulated adipocytokines production in obesity. Hypoxia both inhibits adipocyte differentiation from preadipocytes and macrophage migration from the hypoxic adipose tissue. Upon reaching a hypertrophic threshold beyond the adipocyte fat loading capacity, excess extracellular matrix (ECM) components are deposited, causing fibrosis. HIF-1α initiates the whole pathological process of fibrosis and inflammation in the obese adipose tissue. In addition to stressed adipocytes, hypoxia contributes to immune cell migration and activation which further aggravates adipose tissue fibrosis. Therefore, targeting HIF-1α might be an efficient way to suppress hypoxia-induced pathological changes in the ECM. The fibrosis score of adipose tissue correlates negatively with the body mass index and metabolic parameters. Inducers of browning/beiging adipocytes and adipokines, as well as modulations of matrix remodeling enzyme inhibitors, and associated gene regulators, are potential pharmacological targets for treating obesity.

Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments.

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

Missense mutation Q384K in the APOB gene affecting the large lipid transfer module of apoB reduces the secretion of apoB-100 in the liver without reducing the secretion of apoB-48 in the intestine

Molecular genetic testing of patients with hypobetalipoproteinemia may identify a genetic cause that can form the basis for starting proper therapy. Identifying a genetic cause may also provide novel data on the structure-function relationship of the mutant protein. To identify a genetic cause of hypobetalipoproteinemia in a patient with levels of low density lipoprotein cholesterol at the detection limit of 0.1 mmol/l. DNA sequencing of the translated exons with flanking intron sequences of the genes adenosine triphosphate-binding cassette transporter 1, angiopoietin-like protein 3, apolipoprotein B, apolipoprotein A1, lecithin-cholesterol acyltransferase, microsomal triglyceride transfer protein and proprotein convertase subtilisin/kexin type 9. The patient was homozygous for mutation Q384K (c.1150C>A) in the apolipoprotein B gene, and this mutation segregated with hypobetalipoproteinemia in the family. Residue Gln384 is located in the large lipid transfer module of apoB that has been suggested to be important for lipidation of apolipoprotein B through interaction with microsomal triglyceride transfer protein. Based on measurements of serum levels of triglycerides and apolipoprotein B-48 after an oral fat load, we conclude that the patient was able to synthesize apolipoprotein B-48 in the intestine in a seemingly normal fashion. Our data indicate that mutation Q384K severely reduces the secretion of apolipoprotein B-100 in the liver without reducing the secretion of apolipoprotein B-48 in the intestine. Possible mechanisms for the different effects of this and other missense mutations affecting the large lipid transfer module on the two forms of apoB, are discussed.

Effect of Obesity on Lung Function in the Pediatric and Adult Populations with Asthma: A Review.

Obesity and asthma are major global health concerns, particularly in industrialized nations. Obesity has been shown to have detrimental effects on the respiratory system and lung function owing to metabolic issues and immunological consequences. Research has indicated that obese patients with asthma (atopic or T2-high and non-atopic or T2-low) have diminished lung function in terms of functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV), the FEV1/FVC ratio, and FEF 25-75% due to mechanical fat loading on the diaphragm and central adiposity when compared to non-obese asthmatic patients. Therefore, it is plausible that changes in lung function are the result of a combination of mechanical (fat loading on the diaphragm, central adiposity, bronchial hyper-reactivity, and an increase in cholinergic tone), environmental (diet and exercise), and inflammatory factors (local and systemic), which can lead to the obesity-related asthma phenotype characterized by severe asthma symptoms, poor response to corticosteroid treatment, loss of lung function, and poor quality of life from an early age.

Composition and distribution of lipoproteins after evolocumab in familial dysbetalipoproteinemia: A randomized controlled trial

Proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibodies (mAbs) reduce fasting and post fat load cholesterol in non-HDL and intermediate density lipoprotein (IDL) in familial dysbetalipoproteinemia (FD). However, the effect of PCSK9 mAbs on the distribution and composition of atherogenic lipoproteins in patients with FD is unknown. To evaluate the effect of the PCSK9 mAb evolocumab added to standard lipid-lowering therapy in patients with FD on fasting and post fat load lipoprotein distribution and composition. Randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. Patients received an oral fat load at the start and end of each treatment period. Apolipoproteins (apo) were measured with ultracentrifugation, gradient gel electrophoresis, retinyl palmitate and SDS-PAGE. PCSK9 mAbs significantly reduced particle number of all atherogenic lipoproteins, with a stronger effect on smaller lipoproteins than on larger lipoproteins (e.g. IDL-apoB 49%, 95%confidence interval (CI) 41-59 and very low-density lipoprotein (VLDL)-apoB 33%, 95%CI 16-50). Furthermore, PCSK9 mAbs lowered cholesterol more than triglyceride (TG) in VLDL, IDL and low-density lipoprotein (LDL) (e.g. VLDL-C 48%, 95%CI 29-63%; and VLDL-TG 20%, 95%CI 6.3-41%). PCSK9 mAbs did not affect the post fat load response of chylomicrons. PCSK9 mAbs added to standard lipid-lowering therapy in FD patients significantly reduced lipoprotein particle number, in particular the smaller and more cholesterol-rich lipoproteins (i.e. IDL and LDL). PCSK9 mAbs did not affect chylomicron metabolism. It seems likely that the observed effects are achieved by increased hepatic lipoprotein clearance, but the specific working mechanism of PCSK9 mAbs in FD patients remains to be elucidated.

Effect of a Farnesoid X-receptor Agonist on Postprandial Lipemia in Rats Fed a Supraphysiological Fat Dozes

Introduction. One of the most progressive directions of the modern stage of development of biology is the deepening of knowledge about the mechanisms of regulation of metabolic processes, in particular about signal molecules that transmit information to the cell through ion channels and nuclear receptors associated with G-protein or with enzymatic activity. The nuclear Farnesoid X receptor (FXR) is mainly expressed in the liver and intestines, it regulates key genes that provide the processes of synthesis, transport and reabsorption of bile acids, and is also involved in the metabolism of lipids and carbohydrates.Aim. To evaluate the effect of a farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat diet.Materials and methods. An experimental, prospective, controlled, unblinded, randomized study was conducted to study the effect of a farnesoid X receptor agonist (obeticholic acid) on postprandial lipemia in rats receiving a diet containing a supraphysiological dose of fats.Results and discussion. It has been shown that when assessing postprandial lipemia, an oral test for tolerance to supraphysiological doses of fat with the determination of the initial lipid profile parameters and 4 hours after exercise has a sufficiently high information content. It was found that in animals that received a diet containing an increased amount of fat for 28 days, there was an imbalance in lipid metabolism with activation of their absorption in the intestine, but a "slow" reaction of the mechanisms of intermediate lipid metabolism, which was accompanied by the accumulation of triglycerides and cholesterol in the blood of hungry rats, chylomicrons and LDL. At 4 hours post-feeding, these animals showed abnormal increases in triglycerides and cholesterol.Conclusion. The use of obeticholic acid harmonizes lipid metabolism against the background of alimentary fat load, due to the activation of farnesoid X-receptors of the intestine and liver, which is manifested by a simultaneous increase in the intensity of lipid absorption processes and their intermediate metabolism. As a result, the risk of hyperchylomicronemia, hypercholesterolemia and hypertriglyceridemia is eliminated, the likelihood of developing secondary hyperlipedemia, insulin tolerance and functional overload (or pathology) of the liver is reduced.

The Implementation and Testing of a Reliable and Valid Oral Fat Tolerance Test (OFTT) for Research and Clinical Purposes

Background: Increased fat intake leads to a greater risk of atherosclerosis due to the increase in circulating triglycerides (TG), which damages the endothelial lining. An oral fat tolerance test (OFTT) is usually employed to evaluate postprandial lipid metabolism. However, there has yet to be a standardized procedure for doing an OFTT. This investigation assists in the determination of a standardized, reliable, and valid OFTT. Methods: All participants (n=20) were free of any known cardiovascular or metabolic disease. Participants were allotted 20 minutes to complete the OFTT. Baseline and subsequent blood analyses postfeeding were collected at 1, 2, 3, and 4 hours. One of the three OFTT loads of varying fat concentrations was administered to each participant in a randomized crossover design, containing fat loads of 150 g, 100 g, and 50 g of fat. A single-measure consistency intraclass correlation coefficient was used to determine significance (r>0.75). Results: The test-retest reliability of the OFTT loads (150 g, 100 g, and 50 g) were all significant (p<0.001), with ICC at 0.745, 0.923, and 0.715, respectively. Face Validity was confirmed upon repeat analysis. Conclusions: The 100 g OFTT load was the most reliable and valid measure for observing TG elevation. It is proposed that the 100 g load would be a reliable tool for further research investigation and eventual use for clinical purposes.

Neurotensin Gene rs2234762 C>G Variant Associates with Reduced Circulating Pro-NT Levels and Predicts Lower Insulin Resistance in Overweight/Obese Children.

Neurotensin (NT) is a small protein implicated in the regulation of energy balance which acts as both a neurotransmitter in the central nervous system and as a gastrointestinal peptide. In the gut, NT is secreted after fat ingestion and promotes the absorption of fatty acids. The circulating levels of its precursor, pro-NT, predicts the presence and development of metabolic and cardiovascular diseases. Despite the extensive knowledge on the dynamic changes that occur to pro-NT = after fat load, the determinants of fasting pro-NT are unknown. The aim of this study was to determine the possible genetic regulation of plasma pro-NT. The NT gene (NTS) was sequenced for potential functional variants, evaluating its entire genomic and potentially regulatory regions, in DNA from 28 individuals, stratified by low and high pro-NT levels. The identified variant differently distributed in the two pro-NT subgroups was genotyped in a cohort of nine hundred and thirty-two overweight/obese children and adolescents. A total of seven sequence variations across the NTS gene, none of them located in coding regions, were identified. The rs2234762 polymorphism, sited in the NTS gene promoter, was statistically more frequent in the lowest pro-NTS level group. Carriers of the rs2234762 variant showed lower pro-NT levels, after adjusting for sex, age, BMI, triglycerides and the Tanner stage. Having NTS rs2234762 predicted less pronounced insulin resistance at the 6.5-year follow-up with OR: 0.46 (0.216-0.983), at the logistic regression analysis adjusted for age, sex and BMI. In conclusion, the NTS rs2234762 gene variant is a determinant of reduced circulating pro-NT levels in overweight and obese children, which predisposes this group to a more favorable metabolic profile and a reduced insulin resistance later in life, independently from metabolic confounders.

Effect of omega-3 fatty acid ethyl esters on postprandial arterial elasticity in patients with familial hypercholesterolemia

Impaired arterial elasticity reflects increased risk of atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH). Treatment with omega-3 fatty acid ethyl esters (ω-3FAEEs) in FH patients has been shown to improve postprandial triglyceride-rich lipoprotein (TRL) metabolism, including TRL-apolipoprotein(a) [TRL-apo(a)]. Whether ω-3FAEE intervention also improves postprandial arterial elasticity in FH has not been demonstrated. We carried out an 8-week open-label, randomized, crossover trial to test the effect of ω-3FAEEs (4g/day) on postprandial arterial elasticity in 20FH subjects following ingestion of an oral fat load. Fasting and postprandial large (C1) and small (C2) artery elasticity at 4 and 6h were measured by pulse contour analysis of the radial artery. The area under-the-curves (AUCs) (0-6h) for C1, C2, plasma triglycerides and TRL-apo(a) were determined using the trapezium rule. Compared with no treatment, ω-3FAEEs significantly increased fasting (+9%, P<0.05) and postprandial C1 at 4h (+13%, P<0.05) and at 6h (+10%, P<0.05), with improvement in the postprandial C1 AUC (+10%, P<0.01). ω-3FAEEs also decreased postprandial triglyceride and TRL-apo(a) AUCs (-17% and-19%, respectively, P<0.05). ω-3FAEEs had no significant effect on fasting and postprandial C2. The change in C1 AUC was inversely associated with the changes in the AUC of triglycerides (r=-0.609, P<0.01) and TRL-apo(a) (r=-0.490, P<0.05). High-dose ω-3FAEEs improves postprandial large artery elasticity in adults with FH. Reduction in postprandial TRL-apo(a) with ω-3FAEEs may contribute to the improvement in large artery elasticity. However, our findings need to be confirmed in a larger population. https://www. com/NCT01577056.

PENGARUH PENGGUNAAN BERBAGAI JENIS LITTER TERHADAP BOBOT HIDUP, BOBOT KARKAS, DAN BOBOT LEMAK ABDOMINAL BROILER FASE FINISHER DI OPEN HOUSE

This study aimet to decide the impact of utilizing different sorts of litter on live weight, body weight and stomach fat of finisher work grill chickens in an open house. This examination was led for 24 days from 01 Walk to 24 Walk 2022 in Gading Kulon Town, Dau Area, Malang Rule. The material utilized in this study were 27 DOC unsex oven chickens CP 707 strain, as well as starter and finisher stage grill proportions. The litter materials utilized incorporate rice husks, wood sawdust, and rice straw. This study utilized a totally randomized plan with 3 medicines and 3 replications, and every replication comprised of 3 chickens. The treatment applied was P1 (Rice Husk); P2 (wood sawdust); P3 (rice straw). Live weight, corpse and stomach fat were estimated in the finisher stage (35 days old). The information acquired were dissected by examination of difference (ANOVA). In view of the consequences of the review, it was reasoned that the utilization of wood sawdust litter (P2) goodly affected live weight and corpse weight of finisher stage ovens raised in an open house when contrasted with rice husk (P1) and rice straw (P3), albeit the aftereffects of the review were not fundamentally unique. , the utilization of rice husk litter, wood sawdust, and rice straw didn't influence the stomach fat load of finisher work ovens in open houses.Keywords: Litter, Fisiologi Broiler, Open House

Mechanistic Links Between Obesity and Airway Pathobiology Inform Therapies for Obesity-Related Asthma.

Obesity-related asthma is associated with a high disease burden and a poor response to existent asthma therapies, suggesting that it is a distinct asthma phenotype. The proposed mechanisms that contribute to obesity-related asthma include the effects of the mechanical load of obesity, adipokine perturbations, and immune dysregulation. Each of these influences airway smooth muscle function. Mechanical fat load alters airway smooth muscle stretch affecting airway wall geometry, airway smooth muscle contractility, and agonist delivery; weight loss strategies, including medically induced weight loss, counter these effects. Among the metabolic disturbances, insulin resistance and free fatty acid receptor activation influence distinct signaling pathways in the airway smooth muscle downstream of both the M2 muscarinic receptor and the β2 adrenergic receptor, such as phospholipase C and the extracellular signal-regulated kinase signaling cascade. Medications that decrease insulin resistance and dyslipidemia are associated with a lower asthma disease burden. Leptin resistance is best understood to modulate muscarinic receptors via the neural pathways but there are no specific therapies for leptin resistance. From the immune perspective, monocytes and T helper cells are involved in systemic pro-inflammatory profiles driven by obesity, notably associated with elevated levels of interleukin-6. Clinical trials on tocilizumab, an anti-interleukin antibody, are ongoing for obesity-related asthma. This armamentarium of therapies is distinct from standard asthma medications, and once investigated for its efficacy and safety among children, will serve as a novel therapeutic intervention for pediatric obesity-related asthma. Irrespective of the directionality of the association between asthma and obesity, airway-specific mechanistic studies are needed to identify additional novel therapeutic targets for obesity-related asthma.

Effect of evolocumab on fasting and post fat load lipids and lipoproteins in familial dysbetalipoproteinemia

Familial dysbetalipoproteinemia (FD) is the second most common monogenic lipid disorder (prevalence 1 in 850-3500), characterized by postprandial remnant accumulation and associated with increased cardiovascular disease (CVD) risk. Many FD patients do not achieve non-HDL-C treatment goals, indicating the need for additional lipid-lowering treatment options. To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in patients with FD. A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. At the start and end of each treatment period patients received an oral fat load. The primary endpoint was the 8-hour post fat load non-HDL-C area under the curve (AUC). Secondary endpoints included fasting and post fat load lipids and lipoproteins. In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an Ɛ2Ɛ2 genotype. Evolocumab reduced the 8-hour post fat load non-HDL-C AUC with 49% (95%CI 42-55) and apolipoprotein B (apoB) AUC with 47% (95%CI 41-53). Other fasting and absolute post fat load lipids and lipoproteins including triglycerides and remnant-cholesterol were also significantly reduced by evolocumab. However, evolocumab did not have significant effects on the rise above fasting levels that occurred after consumption of the oral fat load. Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and absolute post fat load concentrations of non-HDL-C, apoB and other atherogenic lipids and lipoproteins in FD patients. The clinically significant decrease in lipids and lipoproteins can be expected to translate into a reduction in CVD risk in these high-risk patients.

126 CENTRAL ADIPOSITY IS ASSOCIATED WITH INCREASED PREVALENCE OF VERTEBRAL FRACTURES

Abstract Background Increased body weight and obesity are associated with greater bone mineral density (BMD) though effects on fracture risk appear to be site specific. In particular, the relationship between Body Mass Index (BMI), abdominal weight and Vertebral Fractures (VF) is complex. Some studies have found greater incidence of VF's with obesity though results are inconsistent. Recent evidence supports a stronger association between measures of abdominal fat and VF's. We aimed to examine the association between central adiposity and VF's in older Irish adults. Methods Participants were from a large cross-sectional study of older Irish adults (aged &amp;gt;60) attending GP or hospital outpatient services. VF diagnosis was based on self-report (ie. clinical vertebral fracture) so we excluded those with a Mini Mental State Examination (MMSE) &amp;lt; 25. BMD was measured with DXA and patients taking antiresorptive or anabolic therapies were excluded. The relationship of waist hip ratio (a surrogate marker of central adiposity) with VF's was explored in regression models. Results 2055 identified, mean age 69.8 ± 6.3 years (range 60-99), 58.6% female. Vertebral fracture prevalence was 6.3% (n=130). Waist hip ratio was positively associated with presence of a vertebral fracture after adjusting for age, sex, BMI, timed up and go, smoking, serum vitamin D, lumbar spine BMD and steroid use &amp;gt; 3 months (beta: 0.04, P&amp;lt;0.001). Conclusion We identified that central adiposity (as measured by waist/hip ratio) was associated with VF presence independent of several factors including BMI and spine BMD. This suggests that body fat distribution and/or altered bone quality may play a role. Visceral body fat (which is correlated with waist hip ratio) is associated with increased production of adipocytokines, altered vertebral geometry and micro-architecture, increased vertebral bone marrow fat and greater loading forces on the spine, all of which may mediate increased VF risk.

RIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease.

Receptor-interacting protein kinase 3 (RIPK3) mediates NAFLD progression, but its metabolic function is unclear. Here, we aimed to investigate the role of RIPK3 in modulating mitochondria function, coupled with lipid droplet (LD) architecture in NAFLD. Functional studies evaluating mitochondria and LD biology were performed in wild-type (WT) and Ripk3-/- mice fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks and in CRISPR-Cas9 Ripk3 -null fat-loaded immortalized hepatocytes. The association between hepatic perilipin (PLIN) 1 and 5, RIPK3, and disease severity was also addressed in a cohort of patients with NAFLD and in PLIN1 -associated familial partial lipodystrophy. Ripk3 deficiency rescued impairment in mitochondrial biogenesis, bioenergetics, and function in CDAA diet-fed mice and fat-loaded hepatocytes. Ripk3 deficiency was accompanied by a strong upregulation of antioxidant systems, leading to diminished oxidative stress upon fat loading both in vivo and in vitro. Strikingly, Ripk3-/- hepatocytes displayed smaller size LD in higher numbers than WT cells after incubation with free fatty acids. Ripk3 deficiency upregulated adipocyte and hepatic levels of LD-associated proteins PLIN1 and PLIN5. PLIN1 upregulation controlled LD structure and diminished mitochondrial stress upon free fatty acid overload in Ripk3-/- hepatocytes and was associated with diminished human NAFLD severity. Conversely, a pathogenic PLIN1 frameshift variant was associated with NAFLD and fibrosis, as well as with increased hepatic RIPK3 levels in familial partial lipodystrophy. Ripk3 deficiency restores mitochondria bioenergetics and impacts LD dynamics. RIPK3 inhibition is promising in ameliorating NAFLD.

Front-of-pack labeling: a health literacy intervention to improve cardiovascular health in Sub-Saharan Africa

There is a surge in the burden of cardiovascular disease (CVD) in Sub-Saharan African (SSA) countries. Over the last 50 years there has been a rapid growth in the consumption of ultra-processed food products high in salt, fat, and glycemic load in SSA. There is overwhelming evidence linking UPFP consumption to an increased risk of coronary artery disease, cerebrovascular disease, overall CVD, and all-cause mortality. Front-of-pack labeling (FOPL) represents an important intervention to guide consumers towards healthier diets and ultimately contribute to the prevention of diet-related adverse health outcomes including CVD. This paper discusses the challenges in the development and implementation of FOPL systems in SSA, and proposes some key elements that would be critical for developing an effective FOPL system in SSA countries.

The LIPL study lipid panels and platelet activity in coronary heart disease

Abstract Introduction Measuring lipid panel in the fasting state can be inconvenient for patients and may aggravate their compliance. Moreover, people spend most of the day in the nonfasting state. Hence, it suggests that the changes in the process of atherosclerosis happen mainly under the influence of nonfasting lipids. Up to date, the studies in the postprandial state were primarily performed in healthy subjects. Aim This exploratory study investigates the change in lipid profile and platelet activity in patients with different cardiovascular risk profiles in the postprandial state. Methods The studied population consists of 66 patients with different cardiovascular risks: patients with coronary artery disease (CAD) and diabetes mellitus type 2 (DM2) (n=20), CAD without DM2 (n=25), and a healthy control group (n=21). Lipid variables and markers of platelet function were assessed during the fasting state and 3 and 5 hours after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90g of fat. The platelet activity was measured with a Multiplate test using ADP, ASPI and TRAP reagents. Results Patients with CAD and DM2 were significantly older and had the highest BMI. All patients with CAD were on acetylsalicylic acid, and 95% of CAD patients were on high-dose statins. Total cholesterol, LDL-c, Apolipoprotein A1, and Apolipoprotein B did not change during the OFTT, irrespective of the group. However, HDL-c decreased statistically significantly three and five hours after the fat loading with a peak after five hours (3.46±0.4 mg/dL, p&amp;lt;0.001). The lowest HDL-c was in the CAD and DM2 group (p=0.006). Triglycerides (TG) increased significantly during the OFTT, with a peak after 5 hours (130.2±14.5 mg/dL, p&amp;lt;0.001) irrespective of the group. There was no difference in TG concentration between the groups. Differences stayed statistically significant even after adjustment for age and BMI. Platelet activity increased after fat loading, as shown by a significantly increased thrombocyte count after three hours (p&amp;lt;0.001). Platelet activity measured by multiplate test with ADP (7.16±2.17 AU, p=0.005), ASPI (4.60±1.40 AU, p=0.005), and TRAP (11.41±3.10 AU, p=0.001) reagents increased statistically significant three hours after the fat loading. The platelet activity measured by all three reagents remained increased even after the adjustment for age and BMI (ADP: 7.14±2.10 AU, p=0.004, ASPI: 4.60±1.40 AU, p=0.006, TRAP: 11.40±3.10 AU, p=0.002). Moreover, the platelet activity measured by ADP (−13.12±4.93, p=0.030), and TRAP (−14.6±15.51, p=0.031) reagents was lower in the control group. When adjusted for age and BMI, there was no difference in the platelet activity between the three groups. Conclusion This study showed that fatty meal causes worsening of lipid profile and leads to increased platelet activity in subjects irrespective of cardiovascular risk profile. Funding Acknowledgement Type of funding sources: None.

Effect of evolocumab versus placebo added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in familial dysbetalipoproteinemia

Abstract Background Familial Dysbetalipoproteinemia (FD) is the second most common genetic lipid disorder (prevalence ranging from 1 in 1000–2500), characterized by impaired postprandial lipoprotein clearance and associated with increased cardiovascular (CVD) risk. The majority of FD patients do not achieve non-HDL-cholesterol treatment goals, indicating the medical need for additional lipid-lowering treatment options. Purpose To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in FD patients. Methods A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12 week treatment periods. At the start and end of each treatment period FD patients received an oral fat load. The primary endpoint was the 8 hour post fat load non-HDL-cholesterol level expressed as area under the curve (AUC). Levels of other fasting and post fat load lipids and (apo)lipoproteins were assessed with ultracentrifugation, polyacrylamide gels, retinyl palmitate and SDS-PAGE. Results In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an ɛ2ɛ2 genotype. Compared with placebo, evolocumab reduced fasting non-HDL-cholesterol with 51% (95% CI 43–57) and the 8 hours post fat load non-HDL-cholesterol AUC with 49% (95% CI 42–55). Fasting triglyceride levels were reduced with 24% (95% CI 14–37) and the 8 hours post fat load triglyceride AUC was reduced with 22% (95% CI 11–29). Except for HDL-cholesterol, all fasting and 8 hour post fat load lipids and (apo)lipoproteins were significantly reduced by evolocumab, including apolipoprotein B (8 hour post fat load AUC reduction 47% (95% CI 41–53) and remnant cholesterol (8 hour post fat load AUC reduction 49% (95% CI −38 to 59)), compared with placebo. After treatment with evolocumab, 89% of patients achieved their non-HDL-cholesterol treatment goal compared with 36% after placebo. Conclusion Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and post fat load non-HDL-cholesterol and other atherogenic lipids and lipoproteins in FD patients. This is the largest clinical trial in FD to date and the first to investigate evolocumab in this very high-risk group. The large decrease in fasting and post fat load lipids and lipoproteins will likely lower CVD risk in these patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AmgenThis project was funded by Amgen for an investigator-initiated research project. The University Medical Center Utrecht was the sponsor of the study. The financial funder had no role in the design, collection of the data, conduct of the analyses or reporting of the study results.

Nutritional Quality and Safety Characteristics of Imported Biscuits Marketed in Basrah, Iraq

The ingredients and the preparation methods influence biscuit quality and safety. In Iraq, biscuit imports are increasing every year, but no information is available in the scientific literature on their quality and safety features. This work analyzed three types of biscuits (cookies, crackers, and digestives) sampled in the Basrah markets (Iraq) but produced in Spain, Iran, Turkey, and United Arab Emirates. Nine different brands were considered for each country of origin (n = 36), with three replicates per sample. Moisture, ash, fat, proteins, fiber, water activity, peroxide value, 5-hydroxymethyl-2-furfural (HMF), acrylamide, heavy metals, and microbial load were analyzed. All the nutritional parameters were significantly influenced by the variables “Biscuit type” and “Country”. Cookies showed significantly higher fat content and lower protein content than crackers and digestives, as well as higher peroxide value (which was below the limit set by the FAO/WHO within the World Wood Program). Spanish samples had more fat and fewer proteins than biscuits made in other countries. Very high variability was observed in HMF (from not detected to 62.08 mg/kg) and AA content (reaching 1421.8 μg/kg). Cadmium was always absent, and lead was considerably below the allowed limit. Yeasts and molds were above the limits in five samples.