Abstract
Visceral obesity is an important component of metabolic syndrome, a cluster of diseases that also includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function, which manifests as non-alcoholic fatty liver disease (NAFLD). NAFLD is a common cause of abnormal liver function, and numerous studies have established the enormously deleterious role of hepatic steatosis in ischemia-reperfusion (I/R) injury that inevitably occurs in both liver resection and transplantation. Thus, steatotic livers exhibit a higher frequency of post-surgical complications after hepatectomy, and using liver grafts from donors with NAFLD is associated with an increased risk of post-surgical morbidity and mortality in the recipient. Diabetes, another MetS-related metabolic disorder, also worsens hepatic I/R injury, and similar to NAFLD, diabetes is associated with a poor prognosis after liver surgery. Due to the large increase in the prevalence of MetS, NAFLD, and diabetes, their association is frequent in the population and therefore, in patients requiring liver resection and in potential liver graft donors. This scenario requires advancement in therapies to improve postoperative results in patients suffering from metabolic diseases and undergoing liver surgery; and in this sense, the bases for designing therapeutic strategies are in-depth knowledge about the molecular signaling pathways underlying the effects of MetS-related diseases and I/R injury on liver tissue. A common denominator in all these diseases is autophagy. In fact, in the context of obesity, autophagy is profoundly diminished in hepatocytes and alters mitochondrial functions in the liver. In insulin resistance conditions, there is a suppression of autophagy in the liver, which is associated with the accumulation of lipids, being this is a risk factor for NAFLD. Also, oxidative stress occurring in hepatic I/R injury promotes autophagy. The present review aims to shed some light on the role of autophagy in livers undergoing surgery and also suffering from metabolic diseases, which may lead to the discovery of effective therapeutic targets that could be translated from laboratory to clinical practice, to improve postoperative results of liver surgeries when performed in the presence of one or more metabolic diseases.
Highlights
Obesity is the major risk for the development of metabolic syndrome (MetS), a prevalent entity in Western societies that includes cardiovascular risk factors i.e., hypertension, diabetes mellitus, and, insulin resistance (Nakao et al, 2012)
This scenario requires the development of effective strategies to improve post-operative results in non-alcoholic fatty liver disease (NAFLD) and/or diabetic patients subjected to liver surgery; a thorough understanding of the signaling pathways in NAFLD, MetS, diabetes, insulin resistance, and I/R injury are paramount
It has been widely demonstrated that Jun NH(2)terminal kinase (JNK) activation is implicated with steatotic liver damage in transplantation, and warm ischemia alone or combined with resection (Lehmann et al, 2003; Massip-Salcedo et al, 2006; Ben Mosbah et al, 2010; Shaker et al, 2016; Li S. et al, 2017); and, pharmacological regulation of ghrelin has been scarcely explored in liver surgery, first published reports in this regard indicate that treatments increasing hepatic ghrelin levels are harmful in non-steatotic liver grafts from brain dead donor, which represents an experimental model very close to clinical practice (Álvarez-Mercado et al, 2019)
Summary
Obesity is the major risk for the development of metabolic syndrome (MetS), a prevalent entity in Western societies that includes cardiovascular risk factors i.e., hypertension, diabetes mellitus, and, insulin resistance (Nakao et al, 2012). Due to the great increase in the prevalence of NAFLD and diabetes, their association is frequently present in society and in potential liver graft donors, and patients requiring a hepatic resection This scenario requires the development of effective strategies to improve post-operative results in NAFLD and/or diabetic patients subjected to liver surgery; a thorough understanding of the signaling pathways in NAFLD, MetS, diabetes, insulin resistance, and I/R injury are paramount. A better understanding of the molecular mechanisms related to autophagy underlying such conditions is extremely relevant to develop effective therapeutic targets to improve the post-operative outcomes of hepatic surgeries when associated with the mentioned comorbidities In this sense, it is important the knowledge whether the autophagy process is different in livers affected by metabolic comorbidities with and without surgical intervention. The findings that have been reported about the effects of such metabolic diseases on the hepatic autophagy process are presented below
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