Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders,including obesity,type 2 diabetes and non-alcoholic fatty liver disease(NAFLD).NAFLD is a spec...Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders,including obesity,type 2 diabetes and non-alcoholic fatty liver disease(NAFLD).NAFLD is a spectrum of disorders,and starts with simple steatosis,progresses to non-alcoholic steatohepatitis,and then advances to fibrosis,cirrhosis and finally,hepatocellular carcinoma,due to perpetual cycles of insults caused by inflammation and other cellular stress.Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019(COVID-19),and patients with COVID-19 have a higher liver injury and mortality.Although the exact cause or mechanism is not known,inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and is known to be associated with higher mortality among COVID-19 patients.Therefore,the COVID-19 pandemic seems to be a major concern in NAFLD patients,who have contracted SARS-CoV-2 infection and develop COVID-19.This is evident in patients at any stage of the NAFLD spectrum,as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD.Thus,there is a need for resolution of the inflammatory cytokine storm in these patients.A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids(ω-3 LCPUFA)in NAFLD conditions,due to their anti-inflammatory,immunomodulatory and anti-viral properties.Therefore,intervention withω-3 LCPUFA,an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression.Although there are challenges in implementation,optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics;NAFLD and COVID-19 at least in this subset of patients.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a progressive disease and one of the leading causes of death.An unnamed disease has become a global epidemic disease of public health concern.This spectrum of diseases manife...Non-alcoholic fatty liver disease(NAFLD)is a progressive disease and one of the leading causes of death.An unnamed disease has become a global epidemic disease of public health concern.This spectrum of diseases manifests itself with initial accumulation of excessive triglycerides(due to de novo lipogenesis)in the hepatocytes,leading to simple steatosis.Although its aetiology is multi-factorial,lifestyle changes(diet and physical activity)are considered to be the key thriving factors.In this context,high fructose consumption is associated with an increased risk for developing NAFLD in humans,while high-fructose feeding to experimental animals results in hepatic steatosis and non-alcoholic steatohepatitis,by increasing hepatic lipogenesis.Among several lipogenic genes,the endoplasmic reticulum-bound stearoyl-CoA desaturase 1(SCD1)is the key determinant of triglycerides biosynthesis pathway,by providing monounsaturated fatty acids,through the incorporation of a double bond at the delta-9 position of saturated fatty acids,specifically,palmitic(C16:0)and stearic(C18:0)acids,yielding palmitoleic(C16:1)and oleic(C18:1)acids,respectively.Various experimental studies involving SCD1 gene knockout and diet-induced rodent models have demonstrated that SCD1 plays a key role in the development of NAFLD,by modulating hepatic lipogenesis and thus triglyceride accumulation in the liver.Several pharmacological and dietary intervention studies have shown the benefits of inhibiting hepatic SCD1 in the pathogenesis of NAFLD.In this review,we give an overview of SCD1 in NAFLD,based on the current experimental evidence and the translational applicability of SCD1 inhibition in human NAFLD conditions,besides discussing the limitations and way-forward.展开更多
文摘Inflammation is one of the primary factors associated with the causation and/or progression of several lifestyle disorders,including obesity,type 2 diabetes and non-alcoholic fatty liver disease(NAFLD).NAFLD is a spectrum of disorders,and starts with simple steatosis,progresses to non-alcoholic steatohepatitis,and then advances to fibrosis,cirrhosis and finally,hepatocellular carcinoma,due to perpetual cycles of insults caused by inflammation and other cellular stress.Emerging evidence has documented that patients with NAFLD have severe coronavirus disease 2019(COVID-19),and patients with COVID-19 have a higher liver injury and mortality.Although the exact cause or mechanism is not known,inflammatory cytokine storm is a characteristic feature of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and is known to be associated with higher mortality among COVID-19 patients.Therefore,the COVID-19 pandemic seems to be a major concern in NAFLD patients,who have contracted SARS-CoV-2 infection and develop COVID-19.This is evident in patients at any stage of the NAFLD spectrum,as the inflammatory cytokine storm may cause and/or aggravate the progression or severity of NAFLD.Thus,there is a need for resolution of the inflammatory cytokine storm in these patients.A large body of evidence has demonstrated the efficacy of omega-3 long-chain polyunsaturated fatty acids(ω-3 LCPUFA)in NAFLD conditions,due to their anti-inflammatory,immunomodulatory and anti-viral properties.Therefore,intervention withω-3 LCPUFA,an effective pharmaconutrient along with the standard treatment for COVID-19 may be useful in the management of the NAFLD spectrum in COVID-19 patients with pre-existing NAFLD conditions by resolving the inflammatory cytokine storm and thereby attenuating its progression.Although there are challenges in implementation,optimistically they can be circumvented and the pharmaconutrition strategy may be potentially helpful in tackling both the pandemics;NAFLD and COVID-19 at least in this subset of patients.
基金Indian Council of Medical Research(ICMR),No.5/4/3-10/TF/2011/NCD-IIDepartment of Biotechnology(DBT),No.BT/PR6145/FNS/20/566/2012and ICMR-NIN-Intramural Grant.
文摘Non-alcoholic fatty liver disease(NAFLD)is a progressive disease and one of the leading causes of death.An unnamed disease has become a global epidemic disease of public health concern.This spectrum of diseases manifests itself with initial accumulation of excessive triglycerides(due to de novo lipogenesis)in the hepatocytes,leading to simple steatosis.Although its aetiology is multi-factorial,lifestyle changes(diet and physical activity)are considered to be the key thriving factors.In this context,high fructose consumption is associated with an increased risk for developing NAFLD in humans,while high-fructose feeding to experimental animals results in hepatic steatosis and non-alcoholic steatohepatitis,by increasing hepatic lipogenesis.Among several lipogenic genes,the endoplasmic reticulum-bound stearoyl-CoA desaturase 1(SCD1)is the key determinant of triglycerides biosynthesis pathway,by providing monounsaturated fatty acids,through the incorporation of a double bond at the delta-9 position of saturated fatty acids,specifically,palmitic(C16:0)and stearic(C18:0)acids,yielding palmitoleic(C16:1)and oleic(C18:1)acids,respectively.Various experimental studies involving SCD1 gene knockout and diet-induced rodent models have demonstrated that SCD1 plays a key role in the development of NAFLD,by modulating hepatic lipogenesis and thus triglyceride accumulation in the liver.Several pharmacological and dietary intervention studies have shown the benefits of inhibiting hepatic SCD1 in the pathogenesis of NAFLD.In this review,we give an overview of SCD1 in NAFLD,based on the current experimental evidence and the translational applicability of SCD1 inhibition in human NAFLD conditions,besides discussing the limitations and way-forward.
