Consequences Of Hypertriglyceridemia Research Articles

Mechanisms linking hypertriglyceridemia to acute pancreatitis.

Hypertriglyceridemia (HTG) is a metabolic disorder, defined when serum or plasma triglyceride concentration (seTG) is >1.7 mM. HTG can be categorized as mild to very severe groups based on the seTG value. The risk of acute pancreatitis (AP), a serious disease with high mortality and without specific therapy, increases with the degree of HTG. Furthermore, even mild or moderate HTG aggravates AP initiated by other important etiological factors, including alcohol or bile stone. This review briefly summarizes the pathophysiology of HTG, the epidemiology of HTG-induced AP and the clinically observed effects of HTG on the outcomes of AP. Our main focus is to discuss the pathophysiological mechanisms linking HTG to AP. HTG is accompanied by an increased serum fatty acid (FA) concentration, and experimental results have demonstrated that these FAs have the most prominent role in causing the consequences of HTG during AP. FAs inhibit mitochondrial complexes in pancreatic acinar cells, induce pathological elevation of intracellular Ca2+ concentration, cytokine release and tissue injury, and reduce the function of pancreatic ducts. Furthermore, high FA concentrations can induce respiratory, kidney, and cardiovascular failure in AP. All these effects may contribute to the observed increased AP severity and frequent organ failure in patients. Importantly, experimental results suggest that the reduction of FA production by lipase inhibitors can open up new therapeutic options of AP. Overall, investigating the pathophysiology of HTG-induced AP or AP in the presence of HTG and determining possible treatments are needed.

Apolipoprotein M and Sphingosine-1-Phosphate: A Potentially Antidiabetic Tandem Carried by HDL.

The frequent finding of low HDL cholesterol in patients with type 2 diabetes (T2D) or at increased risk for T2D has been traditionally interpreted as the consequence of hypertriglyceridemia and hyperacylemia, which are caused by insulin resistance and hyperinsulinemia (1). However, several observations also point to antidiabetic actions of HDL (1,2). Post hoc analyses of randomized controlled trials showed that inhibitors of cholesteryl ester transfer protein, which increase HDL cholesterol by 25 to 100%, improve the glycemic control of subjects with diabetes and lower the incidence of diabetes in patients who are treated with statins (3). Infusion of artificial reconstituted HDL led to acute decreases in glucose levels and improved insulin sensitivity in subjects with diabetes (4). Mendelian randomization studies generated controversial data, with one study supporting and another disproving genetic causality of HDL for T2D (5,6). Data from genetic mouse models indicate that HDL secures both insulin production in pancreatic β-cells and insulin action in the periphery (2). The clinical exploitation of HDL in the prevention and management of diabetes—for example, the development of drugs that stimulate or mimic the antidiabetic effects of HDL or biomarkers that improve risk prediction—is hampered by the presence of hundreds of different proteins and lipid species in HDL, several of which show antidiabetic properties (7). In this issue of Diabetes , Kurano et al. (8) provide evidence that at least a part of HDL’s antidiabetic action involves apolipoprotein M (apoM) and its lipid ligand sphingosine-1-phosphate (S1P), two quantitatively minor components of HDL. S1P is the …

Hypertriglyceridemia - Common Causes, Prevention and Treatment Strategies.

Background: Prevention and treatment of dyslipidemias represent the key issues of Cardiovascular Disease (CVD) prophylaxis. Consequently, the effective management of different types of lipid disorders, including hypertriglyceridemia, should be a priority for the healthcare practi-tioners (e.g.: cardiology and endocrinology specialists, primary care physicians, dietitians, and phar-macists), who provide medical care, as well as for the patients, who receive this care, and need to be directly engaged in it, in order to improve their outcomes. The aim of this review is to facilitate the translation of current trends in hypertriglyceridemia management into a daily practice. The article fo-cuses on the common causes and consequences of hypertriglyceridemia, and discusses diagnostic evaluation and therapeutic options for patients with high Triglyceride (TG) levels and CVD risk.Conclusion: This review presents the main practice-related strategies, based on the current guidelines for the management of dyslipidemias and CVD risk, according to the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS), and the American College of Cardiology (ACC)/American Heart Association (AHA), including both non-pharmacological, and pharmacologi-cal approaches. It also addresses the beneficial impact of pharmaceutical Care (PC) interventions on clinical outcomes of patients with lipid disorders and CVD risk (in light of Randomized Controlled Trials (RCT) data), and underlines the importance of close cooperation between physicians and phar-macists, who manage such patients.

Mechanisms and consequences of hypertriglyceridemia and cellular lipid accumulation in chronic kidney disease and metabolic syndrome.

Hypertriglyceridemia and intracellular lipid overload are commonly present in both the chronic kidney disease (CKD) and metabolic syndrome. Hypertriglyceridemia in the metabolic syndrome arises mostly from increased lipoprotein synthesis, while that in the CKD is mainly caused by decreased catabolism. In metabolic syndrome, enhanced plasma levels of free fatty acids and triglyceride (TG) may lead to intracellular fatty acid accumulation in the kidney. However, the mechanisms by which intracellular lipid accumulation occurs in the dieased glomeruli have not been established. I provide evidence that binding/uptake of TG-rich very low-density lipoprotein by glomerular cells is increased in CKD, leading to increased endocytic accumulation of TG. I also provide evidence that cellular damage by fatty acid accumulation in the kidney is particularly severe in podocytes, leading to apoptosis and resulting in glomerulosclerosis. Collectively, these data bring new mechanistic insights into cellular lipid overload and lipotoxicity in CKD.

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM.

Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on beta-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/l sodium oleate) or TG (5.0 mmol/l Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the beta-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM