Abstract
Chronic excessive alcohol use is a well-recognized risk factor for pancreatic dysfunction and pancreatitis development. Evidence from in vivo and in vitro studies indicates that the detrimental effects of alcohol on the pancreas are from the direct toxic effects of metabolites and byproducts of ethanol metabolism such as reactive oxygen species. Pancreatic dysfunction and pancreatitis development are now increasingly thought to be multifactorial conditions, where alcohol, genetics, lifestyle, and infectious agents may determine the initiation and course of the disease. In this review, we first highlight the role of nonoxidative ethanol metabolism in the generation and accumulation of fatty acid ethyl esters (FAEEs) that cause multi-organellar dysfunction in the pancreas which ultimately leads to pancreatitis development. Further, we discuss how alcohol-mediated altered autophagy leads to the development of pancreatitis. We also provide insights into how alcohol interactions with other co-morbidities such as smoking or viral infections may negatively affect exocrine and endocrine pancreatic function. Finally, we present potential strategies to ameliorate organellar dysfunction which could attenuate pancreatic dysfunction and pancreatitis severity.
Highlights
Based on a 2018 report from the World Health Organization (WHO), alcohol abuse accounted for ~3 million deaths (5.3% of all deaths) worldwide in 2016 [1], and in the United States alone an estimated economic cost for excessive alcohol use was $249 billion in 2010 [2]
A meta-analysis study of 51 international population-based reported studies [37], concluded that heavy alcohol use (>20 drinks per week on a regular basis) increases the risk of pancreatic diseases by nearly 40% compared to non-heavy, alcohol users; and the risk is modified by other co-factors including smoking, obesity, and diet habits
In this review we discuss the recent advances in understanding the complexity of alcohol-induced pancreatic dysfunction and development of alcoholic pancreatitis under the following pathophysiological themes: Biomolecules 2020, 10, 669 (i) Metabolic basis for alcoholic pancreatitis (ii) Role of the UPR in the development of alcoholic pancreatitis (iii) Role of impaired autophagy in the pathogenesis of alcoholic pancreatitis (iv) Chronic alcohol consumption dysregulates pancreatic endocrine function and exacerbates metabolic alterations in people living with human immunodeficiency virus (HIV)
Summary
Based on a 2018 report from the World Health Organization (WHO), alcohol abuse accounted for ~3 million deaths (5.3% of all deaths) worldwide in 2016 [1], and in the United States alone an estimated economic cost for excessive alcohol use was $249 billion in 2010 [2]. A meta-analysis study of 51 international population-based reported studies [37], concluded that heavy alcohol use (>20 drinks per week on a regular basis) increases the risk of pancreatic diseases by nearly 40% compared to non-heavy, alcohol users; and the risk is modified by other co-factors including smoking, obesity, and diet habits. These reports support the concept that high average alcohol consumption increases the risk of pancreatitis, but more investigations are needed to determine how patterns of drinking, such as short-term and long-term heavy drinking as well as inter- and intra-individual variability affect the onset and clinical progression of AP to CP pathophysiology. (i) Metabolic basis for alcoholic pancreatitis (ii) Role of the UPR in the development of alcoholic pancreatitis (iii) Role of impaired autophagy in the pathogenesis of alcoholic pancreatitis (iv) Chronic alcohol consumption dysregulates pancreatic endocrine function and exacerbates metabolic alterations in people living with human immunodeficiency virus (HIV)
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