The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis

Ou, Horng Yih; Wu, Hung Tsung; Lin, Ching Han; Du, Ye; Hu, Chih-Lin; Hung, Hao Chang; Wu, Pansee; Li, Hung Yuan; Wang, Shu‐Huei; Chang, Chih Jen

doi:10.1210/jc.2016-3287

Cited by 30 publications

(43 citation statements)

References 27 publications

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“…The formation of triacylglycerol‐enriched lipid droplets and induction of autophagy by OLA are protective mechanisms against SFA‐induced lipotoxicity (Mei et al, ). In this study, we provided evidence that OLA‐induced HPS expression might play an important role in the protective effects of unsaturated fatty acids, in consistent with previous study (Ou et al, ). It was known that HPS regulates cell proliferation and protects hepatic cells from chemical‐induced liver injury (Li et al, ).…”

Section: Discussionsupporting

confidence: 92%

Unsaturated Fatty Acids Increase the Expression of Hepassocin through a Signal Transducer and Activator of Transcription 3‐Dependent Pathway in HepG2 Cells

Cheng

Hung

et al. 2018

Lipids

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Hepassocin (HPS) is a hepatokine that regulates hepatocyte proliferation. It is known that HPS plays an important role in the development of nonalcoholic fatty liver diseases (NAFLD). Fatty acids, such as oleic acid (OLA), exhibit the ability to activate the signal transducer and activator of transcription‐3 (STAT3), and the binding site of STAT3 is found in the promoter region of HPS. However, the regulation of HPS by fatty acids is still obscure. To clarify the regulation of HPS, we detected the expression of HPS by western blots. In addition, a hepatic steatosis cell culture model was established by treatment of different fatty acids, including linoleic acid (LNA), oleic acid, palmitic acid, and stearic acid. The intracellular lipid accumulation was confirmed by oil red O staining. Blocking of STAT3 activity was achieved by the pretreatment of the STAT3 inhibitor, stattic. We found that activation of STAT3 by interleukin‐6 (IL‐6) was mediated in the regulation of HPS expression. Treatment of unsaturated fatty acids significantly induced intracellular lipid accumulation in HepG2 cells. Moreover, the expressions of HPS were increased in unsaturated fatty acid‐treated HepG2 cells, as compared with saturated fatty acid‐treated groups. Also, the expression of HPS induced by OLA was blocked by the inhibition of STAT3 activity. Furthermore, we found that deletion of HPS by small interfering ribonucleic acid transfection decreased the protective effect of OLA on cell viability. Taken together, we provided evidence that STAT3 plays an important role in the regulation of OLA‐induced HPS expression and the increased HPS may further participate in the development of NAFLD. In addition, the increase of HPS might be involved in the protective effect of OLA on cell viability.

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Section: Discussionsupporting

confidence: 92%

Unsaturated Fatty Acids Increase the Expression of Hepassocin through a Signal Transducer and Activator of Transcription 3‐Dependent Pathway in HepG2 Cells

Cheng

Hung

et al. 2018

Lipids

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“…FGL1 promotes the proliferation of hepatocytes via an extracellular signal‐regulated kinase 1/2 (ERK1/2)‐dependent autocrine mechanism and exhibited protective effects during liver injury . In addition, FGL1 has a rescue role in hyperglycemic crises . Moreover, we showed that FGL1 has an important role in the development of NAFLD and insulin resistance (IR) .…”

Section: Introductionmentioning

confidence: 93%

“…16 In addition, FGL1 has a rescue role in hyperglycemic crises. 17 Moreover, we showed that FGL1 has an important role in the development of NAFLD and insulin resistance (IR). 18,19 Overexpression of FGL1 in the liver increased hepatic lipid accumulation and IR in mice.…”

Section: Introductionmentioning

confidence: 99%

Targeting fibrinogen‐like protein 1 is a novel therapeutic strategy to combat obesity

Chen

Fan

et al. 2019

FASEB j.

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Fibrinogen‐like‐protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2; n = 134) or without obesity (BMI <25 kg/m2; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1‐knockdown by lentiviral vector encoding short‐hairpin RNA targeted to FGL1 decreased high‐fat diet‐induced adiposity. In addition, 3T3‐L1 adipocytes were used to clarify the possible mechanism of FGL1‐induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2‐C/EBPβ‐dependent pathway in 3T3‐L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.

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“…Under normal physiological conditions, FGL1 is secreted mainly by hepatocytes in the liver (some of which may also exist in the pancreas) [50]. It is now clear that FGL1 is the product of hepatocyte regeneration and participates in hepatocyte mitosis and liver energy utilization (including lipid metabolism and blood glucose regulation) [54,68,69]. Apart from the above functions, FGL1 can also be detected in the plasma as an acute reactant [70], implying that FGL1 secreted by the liver acts not only on hepatocytes (autocrine) but also on other tissues, such as muscle and brown adipose tissues (telecrine) (Fig.…”

Section: Structure and Distribution Of Fgl1mentioning

confidence: 99%

“…Under stimulation by metabolic factors (hyperglycemia, hyperlipidemia, hormones, etc. ), the liver secretes FGL1 and participates in the blood circulation [52,69,71]. This function of FGL1 acts on brown adipose tissue [54,56], regulates body productivity and maintains body temperature.…”

Section: Structure and Distribution Of Fgl1mentioning

confidence: 99%

Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target

Zhao

Wang

et al. 2021

J Hematol Oncol

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Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment.

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The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis

Abstract: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.

Cited by 30 publications

References 27 publications

Unsaturated Fatty Acids Increase the Expression of Hepassocin through a Signal Transducer and Activator of Transcription 3‐Dependent Pathway in HepG2 Cells

Unsaturated Fatty Acids Increase the Expression of Hepassocin through a Signal Transducer and Activator of Transcription 3‐Dependent Pathway in HepG2 Cells

Targeting fibrinogen‐like protein 1 is a novel therapeutic strategy to combat obesity

Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target

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