Mechanisms linking hypertriglyceridemia to acute pancreatitis

Abstract

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.

Elevated serum high triglyceride-glucose index is Independently Associated with poor prognosis in patients with acute pancreatitis

“…Consequently, AP-related adverse events like pancreatic necrosis, organ failure, and disease deterioration were accompanied by MS. Furthermore, hyperglycemia and hypertriglyceridemia are the major components of the TyG index and have been observed effects on the severity of AP [25,26]. Experimental and epidemiological studies demonstrated that hypertriglyceridemia not only causes AP but can also modify its severity.…”

“…Hypertriglyceridemia can be hydrolyzed to fatty acids by lipases, which can inhibit mitochondrial function in pancreatic acinar cells, and induce a pathological elevation of intracellular Ca 2+ concentration, cytokine release, and tissue injury [25]. Clinically, the higher the serum hypertriglyceridemia, the greater the likelihood of pancreatic necrosis, organ failure, and Systemic In ammatory Response Syndrome in patients with AP [4,27].…”

Acute pancreatitis: pathogenesis and emerging therapies

“…[98][99][100] Additionally, hypertriglyceridemia worsens outcomes in AP, regardless of the initial cause. [101] This effect appears to be increased in obese patients and mice, likely due to lipolysis of intrapancreatic fat. [98] One group found that during AP, pancreatic triglyceride lipase (PNLIP) leaks into visceral adipose tissue, causing excessive lipolysis independent of adipocyteautonomous adipose triglyceride lipase, leading to increased nonesterified fatty acids, more severe organ failure, and reduced survival.…”

Association of fatty pancreas and subclinical atherosclerosis: A cross-sectional analysis

“…Abnormal lipid metabolism: Hypertriglyceridaemia (HTG) is a metabolic disorder, de ned when the serum or plasma triglyceride concentration is > 1.7 mmol/L 14 . Hypercholesterolaemia (HTC) was de ned as a serum cholesterol level > 6.2 mmol/L.…”