Serum lipid and fatty acid profiles are highly changed in patients with alcohol induced acute pancreatitis

Abstract

Background/aims

Hyperlipidemia is one known etiology of acute pancreatitis. Alcohol use is known to induce changes in lipid metabolism and might alter the serum lipid and fatty acid profile. We hypothesized that these changes may explain individual susceptibility of developing acute pancreatitis. We compared lipid and fatty acid profiles of patients with acute alcoholic pancreatitis and alcoholic controls.

Methods

19 patients with their first alcoholic pancreatitis and 20 controls were included. Late follow-up samples were obtained from 16 patients. Serum lipids were analyzed enzymatically and the fatty acid profile using gas chromatography.

Results

The concentrations of serum total cholesterol, LDL-cholesterol and HDL-cholesterol were markedly lower in patients than in controls during the acute disease but normalized after follow-up. Patients had statistically significantly lower fatty acid proportions of saturated C14:0, polyunsaturated C18:2, C18:3 and C20:3 of the n-6-series and C18:3 of the n-3-series than controls. In contrast, patients had higher percentages of saturated C16:0 and monounsaturated C18:1n9 fatty acids than controls. Mead acid, C20:3n9, marker of essential fatty acid deficiency, was lower in patients than in controls. C14:0, C20:3n6, C18:3n3 and C20:3n9 remained altered after follow-up.

Conclusion

Serum lipid and fatty acid levels were significantly altered during the acute disease and returned toward normal after 18–24 months, suggesting that the changes are secondary to acute pancreatitis. They are unlikely to be the much sought ‘trigger factor’ of pancreatic necro-inflammation. However, further studies are warranted to fully establish this point.

Introduction

Acute pancreatitis is a significant cause of morbidity and mortality world-wide. Besides gallstones, its main cause is alcohol. Together they account for the majority of all cases, 75–90% [1], [2], [3].

The mechanisms by which alcohol causes acute pancreatitis are still far from clear. The metabolites of ethanol; acetaldehyde and fatty acid ethyl esters, and the release of free radicals associated with ethanol oxidation, may cause acinar insult [4], [5] and induce transcription factors NF-κB and AP-1 that mediate the production of proinflammatory cytokines [6]. Fatty acid ethyl esters cause elevations in the intracellular calcium concentrations that can result to premature digestive enzyme activation, activation of the proinflammatory cascade and even cell death [7], [8]. Although the risk of developing the first pancreatitis is thought to increase concomitantly with the amount of alcohol ingested [9], only a small proportion of all alcoholics ever develop acute pancreatitis [10]. Therefore individual differences have been sought to explain the varying susceptibility, but without success.

Alcohol use is known to induce changes in lipid metabolism in many ways although acute and chronic effects differ [11]. Together with metabolic syndrome, alcohol is the leading cause of hypertriacylglycerolemia [12], [13]. It increases serum HDL-cholesterol levels and synthesis of triacylglycerols and VLDL particles in the liver [11], [14], [15]. Heavy, chronic alcohol use, however, is associated with increased lipoprotein lipase activity and subsequently increased VLDL turnover rate and decreased serum LDL-cholesterol levels [15], [16], [17], [18].

The fatty acid composition of serum lipoproteins and cellular membranes is determined by both dietary intake and endogenous metabolism. Heavy alcohol use might be associated with poor nutrition which in turn might change the serum fatty acid profile [19], [20], [21]. The simplest of the polyunsaturated fatty acids, linoleic acid (18:2n6) and α-linolenic acid (18:3n3) cannot be synthesized by the human body and hence must be obtained from the diet. All long chain fatty acids are modified by the same set of enzymes, stearoyl-CoA desaturase (delta-9 desaturase), delta-5 and delta-6 desaturases and elongation reactions in the tissues, especially the liver, that give rise to longer and more highly unsaturated derivative fatty acids. Some 20-carbon polyunsaturated fatty acids, especially arachidonic acid, serve as precursors for synthesis of eicosanoids which regulate various cellular responses [22].

Alcohol abuse might interfere with fatty acid metabolic pathways. Pawlosky and Salem reported a lower total amount of fatty acids and that of many nonessential and essential (16:0, 18:0, 18:1n9, 18:2n6, 18:3n6, 20:3n6, 18:3n3, 22:5n3 and 22:6n3) fatty acids in the liver of patients with alcohol liver disease than in controls [23]. They also reviewed studies addressing the mechanisms by which alcohol might cause changes in the fatty acid metabolism. Shortly, while in vitro studies indicated that prolonged alcohol use might decrease the delta-5 and delta-6 desaturase activities, which are involved in the desaturation of fatty acids, in vivo the use of alcohol led to higher production of polyunsaturated fatty acids. The lower amount of tissue polyunsaturated fatty acids might be due to the increased rate of catabolism caused by lipid peroxidation. In turn, Boros et al. studied the tissue composition and metabolic rates of certain fatty acids in the liver, pancreas and serum in rats with chronic ethanol consumption [24]. They report increased desaturase activity and fatty acid uptake in the pancreas and lower desaturase activity together with decreased synthesis and transportation of unsaturated C16:0, C18:0 and C18:1n9 fatty acids in the liver associated with chronic ethanol consumption. Marosvolgyi et al. studied the serum fatty acid profile in patients with chronic alcoholic pancreatitis and reported higher percentages of monounsaturated fatty acids and lower levels of arachidonic acid in patients with chronic pancreatitis than in controls [25].

The serum fatty acid profiles have not been previously studied in patients with alcohol induced acute pancreatitis. We hypothesized that the fatty acid profiles differ in patients who developed acute pancreatitis from those with high alcohol consumption but without pancreatitis. The objective of this study was to measure the fatty acid and lipid profiles in patients hospitalized for their first alcohol induced acute pancreatitis during the course of the acute disease and after discharge and follow-up in comparison with control subjects who had high alcohol use but no history of pancreatitis.