Increased brain-derived neurotrophic factor in the serum of persons with nonalcoholic fatty liver disease

Hattori, Yorito; Yamada, Hiroya; Munetsuna, Eiji; Ando, Yoshitaka; Mizuno, Genki; Fujii, Ryosuke; Tsuboi, Yoshiki; Ichino, Naohiro; Osakabe, Keisuke; Sugimoto, Keiko; Ishikawa, Hiroaki; Ohashi, Koji; Suzuki, Kôji

doi:10.1507/endocrj.ej21-0584

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Moreover, BDNF has been proposed to act as a connection between the central nervous system and peripheral organs through regulating energy intake and expenditure and to exert pleiotropic effects in the periphery beyond the central nervous system [36,42]. In a cross-sectional study, Hattori et al recently reported high levels of serum BDNF in NAFLD [43]. The authors of that study speculated that the elevation of serum BDNF levels might be a compensatory response aimed at counteracting abnormal glucose and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Brain‐derived neurotrophic factor knock‐out mice develop non‐alcoholic steatohepatitis

Ichimura‐Shimizu,

Kojima,

Suzuki

et al. 2023

The Journal of Pathology

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While brain‐derived neurotrophic factor (BDNF), which is a growth factor associated with cognitive improvement and the alleviation of depression symptoms, is known to regulate food intake and body weight, the role of BDNF in peripheral disease is not fully understood. Here, we show that reduced BDNF expression is associated with weight gain and the chronic liver disease non‐alcoholic steatohepatitis (NASH). At 10 months of age, BDNF‐heterozygous (BDNF+/−) mice developed symptoms of NASH: centrilobular/perivenular steatosis, lobular inflammation with infiltration of neutrophils, ballooning hepatocytes, and fibrosis of the liver. Obesity and higher serum levels of glucose and insulin – major pathologic features in human NASH – were dramatic. Dying adipocytes were surrounded by macrophages in visceral fat, suggesting that chronic inflammation occurs in peripheral organs. RNA sequencing (RNA‐seq) studies of the liver revealed that the most significantly enriched Gene Ontology term involved fatty acid metabolic processes and the modulation of neutrophil aggregation, pathologies that well characterise NASH. Gene expression analysis by RNA‐seq also support the notion that BDNF+/− mice are under oxidative stress, as indicated by alterations in the expression of the cytochrome P450 family and a reduction in glutathione S‐transferase p, an antioxidant enzyme. Histopathologic phenotypes of NASH were also observed in a knock‐in mouse (BDNF+/pro), in which the precursor BDNF is inefficiently converted into the mature form of BDNF. Lastly, as BDNF reduction causes overeating and subsequent obesity, a food restriction study was conducted in BDNF+/pro mice. Pair‐fed BDNF+/pro mice developed hepatocellular damage and showed infiltration of inflammatory cells, including neutrophils in the liver, despite having body weights and blood parameters that were comparable to those of controls. This is the first report demonstrating that reduced BDNF expression plays a role in the pathogenic mechanism of NASH, which is a hepatic manifestation of metabolic syndrome. © 2023 The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Brain‐derived neurotrophic factor knock‐out mice develop non‐alcoholic steatohepatitis

Ichimura‐Shimizu,

Kojima,

Suzuki

et al. 2023

The Journal of Pathology

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“…Xu et al [ 165 ] found that BDNF expression appears to require activity of the MyD88/NF- κ B signaling pathway to induce innate immune responses which also induces innate immune responses [ 165 ]. BDNF is an important marker for preventing and treating NAFLD [ 166 ], as its serum level has positive association with NAFLD [ 167 ]. However, no in vitro or in vivo experiments have found the signaling pathway between BNDF and NAFLD.…”

Section: Myokines and Nf- κ B Activationmentioning

confidence: 99%

Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease

Yang

Tan

et al. 2022

Canadian Journal of Gastroenterology and Hepatology

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The pathogenesis of NAFLD is complex and diverse, involving multiple signaling pathways and cytokines from various organs. Hepatokines, stellakines, adipokines, and myokines secreted by hepatocytes, hepatic stellate cells, adipose tissue, and myocytes play an important role in the occurrence and development of nonalcoholic fatty liver disease (NAFLD). The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) contributes to the progression of NAFLD by mediating liver inflammation, immune response, hepatocyte death, and later compensatory proliferation. In this review, we first discuss the crosstalk and interaction between hepatokines, stellakines, adipokines, and myokines and NF-κB in NAFLD. The characterization of the crosstalk of NF-κB with these factors will provide a better understanding of the molecular mechanisms involved in the progression of NAFLD. In addition, we examine new expert management opinions for NAFLD and explore the therapeutic potential of silymarin in NAFLD/NASH.

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Myokines and Their Potential Protective Role Against Oxidative Stress in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Bucarey,

Trujillo-González,

Paules

et al. 2024

Antioxidants

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Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver’s antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health.

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Increased brain-derived neurotrophic factor in the serum of persons with nonalcoholic fatty liver disease

Cited by 3 publications

References 32 publications

Brain‐derived neurotrophic factor knock‐out mice develop non‐alcoholic steatohepatitis

Brain‐derived neurotrophic factor knock‐out mice develop non‐alcoholic steatohepatitis

Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease

Myokines and Their Potential Protective Role Against Oxidative Stress in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

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