Cognitive Performance in Individuals With Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes Mellitus

Weinstein, Ali A.; Avila, Leyla de; Paik, James; Golabi, Pegah; Escheik, Carey; Gerber, Lynn H.; Younossi, Zobair M.

doi:10.1016/j.psym.2018.06.001

Cited by 37 publications

(51 citation statements)

References 22 publications

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“…NAFLD prevalence has increased, and over the next 10 years NAFLD is expected to be the leading cause of liver pathology in the Western world; NAFLD can progress to liver failure and, consequently, the need for liver transplantation . NAFLD is recognized as the predominant form of chronic liver disease associated with MS, which includes hypertension, type 2 diabetes mellitus (T2DM), obesity, and hyperlipidemia . While NAFLD is mostly benign, chronic liver inflammation in NASH may cause progression to fibrosis and hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal–Regulating Kinase 1 Pathways

Huang

Zhang

et al. 2019

Hepatology

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Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFDinduced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogenactivated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD. (Hepatology 2019;70:1099-1118). SEE EDITORIAL ON PAGE 1091N onalcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease and is characterized by lipid accumulation in hepatocytes in the absence of excessive alcohol consumption. (1) The prevalence of NAFLD increases worryingly with obesity and other diseases of metabolic syndrome (MS) and is expected to be the leading cause of liver failure in the future. (2) Accumulating studies show that NAFLD not only is linked to an increased risk of liver-related mortality or morbidity

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Section: Discussionmentioning

confidence: 99%

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal–Regulating Kinase 1 Pathways

Huang

Zhang

et al. 2019

Hepatology

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“…A few human studies have sought to objectively characterize cognitive deficits in NAFLD using various neuropsychological tests on a scale that allows adjustment of important confounders [30,31,33,34,36]. These neuropsychological tests and the cognitive domains that they assess are outlined in Table 1 and further described in Table S1.…”

Section: Methods Used To Characterize Cognition In Nafldmentioning

confidence: 99%

“…However, the latter deficits were not significant after adjustment for life-style related confounders. used NHANES data from 2011 to 2014, comprising 1102 subjects above 60 years of age whereof 413 were diagnosed with NAFLD [31]. In this study, a lone NAFLD diagnosis was not associated with poor performance on any of the cognitive tests, whereas NAFLD with concurrent type 2 diabetes mellitus (T2DM) was associated with impaired visuospatial function (DSST).…”

Section: Evidence For Cognitive Dysfunction In Nafldmentioning

confidence: 99%

“…One major limitation of the above studies is the lack of biopsy confirmation. Instead, NAFLD was diagnosed by combinations of ultrasound, computed tomography (CT) imaging and various fibrosis/fatty liver scores [30,31,33]. Accordingly, it is unknown how the severity of NAFLD, e.g., steatohepatitis or hepatic fibrosis, impacts cognitive function; based on the studies' inclusion criteria, patients with more advanced liver disease most likely comprised only a smaller fraction of the NAFLD groups [1].…”

Section: Suggestsmentioning

confidence: 99%

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Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Kjærgaard

Mikkelsen

Wernberg

et al. 2021

JCM

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Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

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“…These disorders, in turn, may accelerate cognitive declines and contribute to cognitive impairments in older adults [26][27][28][29][30]. Obesity over time also leads to increased risk of heart disease, stroke, liver disease, and type 2 diabetes, which can accelerate cognitive function decline [31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Body mass index across adult life and cognitive function in the American elderly

Zhou

Zhang

Lee

et al. 2020

Aging

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This study aimed to examine the associations of body mass index (BMI) across adult life with cognitive function in 2,637 participants aged 60 years or over from NHANES 2011-2014. The primary outcome was a composite score based on test scores on word list learning, animal naming, and digit symbol substitution. Exposures of interest included BMI at age 25, BMI 10 years before the survey, BMI at the survey (current BMI), and BMI burden calculated from age 25 to age at survey. BMI at age 25 was inversely associated with the composite score (β=-0.0271±0.0130 per kg/m 2 , P=0.038) and positively with low cognitive performance (odd ratio=1.04, 95% confidence interval: 1.01-1.07, P=0.010), defined as below 20 percentile of the composite score. Similar results were observed for BMI 10 years before the survey and BMI burden. Current BMI was positively associated with the composite score (β=0.0369±0.0113, P=0.001) and inversely associated with low cognitive performance (odd ratio=0.96, 95% confidence interval: 0.94-0.99, P=0.004). In conclusion, high BMI in early adult life is associated with low cognitive function in late life, which underscores the importance of a healthy body weight across the life course. The association between BMI and cognitive function at late life requires further investigation.

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Cognitive Performance in Individuals With Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes Mellitus

Cited by 37 publications

References 22 publications

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal–Regulating Kinase 1 Pathways

Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal–Regulating Kinase 1 Pathways

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Body mass index across adult life and cognitive function in the American elderly

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