Cytokines Inhibit Fatty Acid Oxidation in Isolated Rat Hepatocytes

Nachiappan, Vasanthi; Curtiss, D.; Corkey, Barbara E.; Kilpatrick, Laurie E.

doi:10.1097/00024382-199402000-00007

Cited by 68 publications

(39 citation statements)

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“…This and other similar reports [32,40,[45][46][47][48] document the negative effects of inflammatory mediators (cytokines) on peroxisomal structure/ functions of liver and brain. Indeed, using three different animals models, i.e.…”

Section: Discussionsupporting

confidence: 84%

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Contreras

Haq

Uto

et al. 2008

Archives of Biochemistry and Biophysics

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Krabbe's disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/function in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-α and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-α, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalasedependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where the induction of TNF-α and IL-6 compromise peroxisomal structure and function.

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Section: Discussionsupporting

confidence: 84%

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Contreras

Haq

Uto

et al. 2008

Archives of Biochemistry and Biophysics

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“…Our findings are surprising given the strong association between the acute phase response and reduced hepatic fatty acid oxidation. 60 Although it is possible that the acute phase response was not as robust in our study of early cachexia, differences in cytokine production (thus, the acute phase response) between the colon-26 and Walker 256 cachexia models 61,62 may better explain these disparate findings. In summary, in the present study we found PKA-induced lipolysis is enhanced in early cancer cachexia which coincided with elevated total energy expenditure and increased expression of markers of BAT thermogenesis when food intake is considered and the hepatic acute phase response.…”

Section: Discussionmentioning

confidence: 81%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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“…Alcohol and hepatitis C infection 3465 [68] 2 [67] 3 [64] With HCV 26.1 62.6 126 [63] 19.1 53.9 [64] ethanol is metabolized to the mutagenic metabolite acetaldehyde and during that reaction ROS are produced mainly as a byproduct of CYP2E1. Additional mechanisms include the release of cytokines such as TNF-α, which increases free fatty acid release from adipocytes in the periphery of the liver [71] , stimulates lipogenesis in hepatocytes [72] , and inhibits β-oxidation of fatty acids [73] . Chronic ethanol consumption also impairs transport and secretion of triglycerides as VLDL [74] which again leads to an increased hepatic fat accumulation.…”

Section: Alcohol Hcv and Liver Damagementioning

confidence: 99%

Evaluation of standard liver volume formulae for Chinese adults

Shi¹,

Yan²,

Li³

et al. 2009

WJG

105

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Alcoholic liver disease (ALD) and hepatitis C virus (HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world. This review discusses the epidemiology and combined impact of ALD and HCV on the progression of liver disease. ALD and HCV affect the progression of liver disease to liver cirrhosis and hepatocellular carcinoma (HCC) in a synergistic manner. Thus, the risk for HCC increases five times with a daily alcohol consumption of 80 g; in the presence of HCV it is increased 20-fold, and a combination of both risk factors leads to a more than 100-fold risk for HCC development. Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication. Several molecular mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression. They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron. Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liver-secreted systemic iron hormone hepcidin. A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future. For now, it can be generally concluded that HCV-infected patients should abstain from alcohol and alcoholics should be encouraged to participate in detoxification programs.

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Cytokines Inhibit Fatty Acid Oxidation in Isolated Rat Hepatocytes

Cited by 68 publications

References 0 publications

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Psychosine-induced alterations in peroxisomes of twitcher mouse liver

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Evaluation of standard liver volume formulae for Chinese adults

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