Leptin in the Field of Hepatic Fibrosis: A Pivotal or an Incidental Player?

Bethanis, Sotirios; Theocharis, Stamatios

doi:10.1007/s10620-006-9126-0

Cited by 24 publications

(22 citation statements)

References 110 publications

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“…Moreover, hyaluronic acid, collagen IV, TIMP-1, -2-macroglobulin, and TGF1 are correlated with a moderate serious fibrotic state (Lu et al, 2003). In addition, the leptin receptor gene possibly involved in fibrogenesis and hepatic inflammation is up-regulated (Bethanis and Theocharis, 2006). The expression patterns of these genes collectively suggest that a fibrotic state develops during the differentiation program, which may be responsible, at least in part, for differentiation problems.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Pietrangelo¹,

Puglielli²,

Mancinelli³

et al. 2009

Experimental Gerontology

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ular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation. Experimental Gerontology, Elsevier, 2009, 44 (8) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT AbstractSarcopenia is the age-related loss of muscle mass, strength and function. Human muscle proteins are synthesized at a slower rate in the elderly than in young adults, leading to atrophy and muscle mass loss with a decline in the functional capability. Additionally, aging is accompanied by a decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells, in which we previously reported oxidative damage evidences. The aim of the present study was to determine the effects of aging on myoblasts and myotubes obtained from human skeletal muscle, and characterize the transcriptional profile as molecular expression patterns in relation to age-dependent modifications in their regenerative capacity. Our data show that the failure to differentiate does not depend on reduced myogenic cell number, but difficulty to complete the differentiation program. Data reported here suggested the following findings: i) oxidative damage accumulation in molecular substrates, probably due to impaired antioxidant activity and insufficient repair capability, ii) limited capability of elderly myoblasts to execute a complete differentiation program; restricted fusion, possibly due to altered cytoskeleton turnover and extracellular matrix degradation, and iii) activation of atrophy mechanism by activation of a specific FOXO-dependent program.

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Section: Discussionmentioning

confidence: 99%

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Pietrangelo¹,

Puglielli²,

Mancinelli³

et al. 2009

Experimental Gerontology

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“…45 Leptin, one of the major adipokines, is a 16-kDa nonglycosylated protein secreted primarily from the adipocytes of white fat; a minor level of regulated leptin expression also occurs at other sites such as placenta, skeletal muscle, and stomach fundus, and in cultureactivated HSCs. 46 Leptin has been recognized as a profi brogenic hormone in the liver. Niu et al 47 reported that leptin acts directly on liver fi brogenesis by stimulating α1(I) collagen production in activated HSCs.…”

Section: Fibrogenesismentioning

confidence: 99%

Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies

et al. 2008

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Activation of hepatic stellate cells (HSCs) is the dominant event in liver fibrosis. The early events in the organization of HSC activation have been termed initiation. Initiation encompasses rapid changes in gene expression and phenotype that render the cells responsive to cytokines and other local stimuli. Cellular responses following initiation are termed perpetuation, which encompasses those cellular events that amplify the activated phenotype through enhanced growth factor expression and responsiveness. Multiple cells and cytokines play a part in the regulation of HSC activation. HSC activation consists of discrete phenotype responses, mainly proliferation, contractility, fibrogenesis, matrix degradation, chemotaxis and retinoid loss. Currently, antifibrotic therapeutic strategies include inhibition of HSC proliferation or stimulation of HSC apoptosis, downregulation of collagen production or promotion of its degradation, administration of cytokines, and infusion of mesenchymal stem cells. In this review, we summarize the latest advances in our understanding of the mechanisms of HSC activation and possible antifibrotic therapeutic strategies.

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Section: Leptinmentioning

confidence: 99%

“…In particular, activation of the LEPR in hepatic stellate cells leads to increased expression of proinflammatory cytokine MCP-1 and proangiogenic vascular endothelial growth factor (VEGF) and angiopoietin-1 [44]. It was also postulated that leptin acts as a profibrogenic cytokine in sinusoidal microenvironment by acting both on endothelial cells and Kupffer cells [45], as it participates in the development of the liver fibrosis associated with chronic viral infections and with primary biliary cirrhosis [46].The involvement of the leptin in the development of the fibrosis in NAFLD is less obvious; a longitudinal study of NAFLD patients revealed no differences in leptin levels in patients with fibrosis progression and those who did not progress [47]. On the other hand, an increase in expression was found both for LEPR mRNA and its protein in patients with NASH, especially those with fibrosis [48].…”

mentioning

confidence: 99%

Adipokines and melanocortins in the hepatic manifestation of metabolic syndrome: nonalcoholic fatty liver disease

Jarrar¹

2018

Preprint

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Metabolic syndrome is associated with nonalcoholic fatty liver disease and its more aggressive form, nonalcoholic steatohepatitis. Adipokines produced by white adipose tissue possess broad physiological activity and play an important autocrine role in obesity-associated complications, including metabolic syndrome, nonalcoholic fatty liver disease and cardiovascular disease. Various adipokines may have beneficial or harmful effects. Other tissues, particularly stomach and intestine, produce active molecules that can influence the function of adipocytes and, possibly, the levels of adipokine secretion. In some cases, the production sites of these molecules remain unknown. The review focuses on our current understanding of the disease-related effects of the adipokines and the melanocortins on various peripheral tissues, and discusses some of their potential interactions with each other. Potential therapeutic applications are also considered.Expert Rev. Mol. Diagn. 7(2), 195-205 (2007) Multiple facets of metabolic syndromeMetabolic syndrome (MS) was first introduced as a clinical entity by Reaven in 1988 [1]. MS represents a cluster of risk factors commonly associated with central obesity, insulin-resistance, hypertension and elevated triglycerides, as well as decreased high-density lipoprotein cholesterol. In turn, MS is associated with an increased risk of cardiovascular disease and is a common early abnormality in the development of Type 2 diabetes. Additionally, MS plays a well-recognized role in the development of the obstructive sleep apnea, erectile dysfunction, polycystic ovary syndrome and malignant tumors. It is noteworthy that, despite tremendous clinical impact of MS, there is no clear consensus regarding the diagnostic criteria for this important nosological entity. To date, different criteria have been proposed by the WHO, by the third report of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, International Diabetes Federation, European Group for the Study of Insulin Resistance, and American College of Endocrinology. The problem of multiple MS definitions was recently addressed in a joint statement of The American Diabetes Association and the European Association for the Study of Diabetes [2]. The statement and other publications stress the necessity of introduction of additional criteria for MS including concentrations of the proand anti-inflammatory proteins in the serum. It is most likely that the list of the etiological factors driving the development of MS includes abnormalities in visceral adipose tissue or an altered inflammatory background that, in turn, stimulate the development of the secondary complications of MS.Recently, nonalcoholic fatty liver disease (NAFLD) and its more aggressive form, nonalcoholic steatohepatitis (NASH), have come to be regarded as the hepatic manifestation of MS. In this context, insulin resistance (IR) is 196Expert Rev. Mol. Diagn. 7(2), (2007) the key eve...

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Leptin in the Field of Hepatic Fibrosis: A Pivotal or an Incidental Player?

Cited by 24 publications

References 110 publications

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Molecular basis of the myogenic profile of aged human skeletal muscle satellite cells during differentiation

Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies

Adipokines and melanocortins in the hepatic manifestation of metabolic syndrome: nonalcoholic fatty liver disease

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