Pancreatic‐derived factor promotes lipogenesis in the mouse liver: Role of the Forkhead box 1 signaling pathway

Li, Jing; Chi, Yujing; Wang, Chunjiong; Wu, Jing; Yang, Hang; Zhang, Dongjuan; Zhu, Yi; Wang, Nanping; Yang, Jichun; Guan, Youfei

doi:10.1002/hep.24295

Cited by 54 publications

(127 citation statements)

References 38 publications

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“…These include fibroblast growth factor 21 (FGF21), α2-HS-glycoprotein (Fetuin-A), and pancreatic-derived factor (PANDER) (67)(68)(69). Intriguingly, the dysregulation of those hepatokines is closely associated with hepatosteatosis and dyslipidemia (68)(69)(70)(71).…”

Section: Discussionmentioning

confidence: 99%

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Lu¹,

Liu²,

Jiao³

et al. 2014

J. Clin. Invest.

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114

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Periostin neutralizing Ab. The hybridoma cell lines secreting mouse mAb against mouse periostin were generated by Abmart Co., according to the standard hybridoma technique (72). The mouse mAbs were purified by Protein A affinity chromatograph. mAb purity was confirmed by HPLC. The concentrations of the obtained mAbs were measured by Mouse IgG ELISA Quantitation kit (Bethyl Laboratories), following the manufacturer's instructions. The kinetic parameters of the mAbs were determined using a Biacore T100 instrument (Biacore AB). Purified Ab was diluted in saline and injected at a dose of 5 mg/kg into db/db mice for 2 weeks.Statistics. All values are shown as mean ± SEM. Statistical differences were determined by 2-way ANOVA with Bonferroni-adjusted post-test or by 2-tailed Student's t test. A P value less than 0.05 was considered significant.

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Section: Discussionmentioning

confidence: 99%

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Lu¹,

Liu²,

Jiao³

et al. 2014

J. Clin. Invest.

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114

128

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“…PEPCK controls the rate limiting step in gluconeogenesis and suppression is expected under conditions of hyperglycemia and insulin secretion (Hanson & Reshef 1997). ACSL1 is an isozyme of the longchain fatty-acid-coenzyme A ligase family that convert Wilson et al (2010) and Li et al (2011), respectively. PANTG describes summary of results from currently described study free long-chain fatty acids into fatty acyl-CoA esters, and serve a central role in lipid biosynthesis (Ning et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…This model revealed fasting hyperglycemia, hyperinsulinemia, and elevated corticosterone levels. Li et al (2011) derived a similar adenoviral-delivered overexpressing model with different results, and did not observe glucose intolerance, fasting glycemia, or elevated corticosterone levels. However, liver and serum triglyceride content was increased along with serum insulin levels, as compared with WT mice.…”

Section: Introductionmentioning

confidence: 99%

PANDER transgenic mice display fasting hyperglycemia and hepatic insulin resistance

Robert-Cooperman¹,

Dougan²,

Moak³

et al. 2014

Journal of Endocrinology

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PANcreatic-DERived factor (PANDER, FAM3B) is a novel protein that is highly expressed within the endocrine pancreas and to a lesser degree in other tissues. Under glucose stimulation, PANDER is co-secreted with insulin from the b-cell. Despite prior creation and characterization of acute hepatic PANDER animal models, the physiologic function remains to be elucidated from pancreas-secreted PANDER. To determine this, in this study, a transgenic mouse exclusively overexpressing PANDER from the endocrine pancreas was generated. PANDER was selectively expressed by the pancreatic-duodenal homeobox-1 (PDX1) promoter. The PANDER transgenic (PANTG) mice were metabolically and proteomically characterized to evaluate effects on glucose homeostasis, insulin sensitivity, and lipid metabolism. Fasting glucose, insulin and C-peptide levels were elevated in the PANTG compared with matched WT mice. Younger PANTG mice also displayed glucose intolerance in the absence of peripheral insulin sensitivity. Hyperinsulinemic-euglycemic clamp studies revealed that hepatic glucose production and insulin resistance were significantly increased in the PANTG with no difference in either glucose infusion rate or rate of disappearance. Fasting glucagon, corticosterones, resistin and leptin levels were also similar between PANTG and WT. Stable isotope labeling of amino acids in cell culture revealed increased gluconeogenic and lipogenic proteomic profiles within the liver of the PANTG with phosphoenol-pyruvate carboxykinase demonstrating a 3.5-fold increase in expression. This was matched with increased hepatic triglyceride content and decreased p-AMPK and p-acetyl coenzyme A carboxylase-1 signaling in the PANTG. Overall, our findings support a role of pancreatic b-cell-secreted PANDER in the regulation of hepatic insulin and lipogenenic signaling with subsequent impact on overall glycemia.

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“…As previously described, 1.0 3 10 9 plaque-forming unit Ad-ATPSb or Ad-green fluorescent protein (GFP) were injected into the db/db mice via tail vein (15,16). At the third and seventh day after virus injection, oral glucose tolerance tests (OGTTs) were performed.…”

Section: Overexpression Of Atpsb In the Livers Of Diabetic Micementioning

confidence: 99%

“…Mice were orally administered with glucose at the dose of 3 g/kg, and blood glucose levels were monitored at 0, 15, 30, 60, 90 and 120 min after the glucose load using a Freestyle brand glucometer (Roche) by blood collected from the tail (15). The blood glucose concentrations at 0 min were determined as FBG.…”

Section: Ogttsmentioning

confidence: 99%

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

Wang

Chen

et al. 2014

Diabetes

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ATP synthase b subunit (ATPSb) had been previously shown to play an important role in controlling ATP synthesis in pancreatic b-cells. This study aimed to investigate the role of ATPSb in regulation of hepatic ATP content and glucose metabolism in diabetic mice. ATPSb expression and ATP content were both reduced in the livers of type 1 and type 2 diabetic mice. Hepatic overexpression of ATPSb elevated cellular ATP content and ameliorated hyperglycemia of streptozocininduced diabetic mice and db/db mice. ATPSb overexpression increased phosphorylated Akt (pAkt) levels and reduced PEPCK and G6pase expression levels in the livers. Consistently, ATPSb overexpression repressed hepatic glucose production in db/db mice. In cultured hepatocytes, ATPSb overexpression increased intracellular and extracellular ATP content, elevated the cytosolic free calcium level, and activated Akt independent of insulin. The ATPSb-induced increase in cytosolic free calcium and pAkt levels was attenuated by inhibition of P2 receptors. Notably, inhibition of calmodulin (CaM) completely abolished ATPSbinduced Akt activation in liver cells. Inhibition of P2 receptors or CaM blocked ATPSb-induced nuclear exclusion of forkhead box O1 in liver cells. In conclusion, a decrease in hepatic ATPSb expression in the liver, leading to the attenuation of ATP-P2 receptor-CaM-Akt pathway, may play an important role in the progression of diabetes. In past decades, diabetes became one of the major diseases threatening our health, with an estimated global prevalence of 6.4% in 2010 (1). The liver is the key tissue that releases glucose into the circulation in fasting status, and an increase in hepatic glucose production due to insulin deficiency or insulin resistance is the central event in the development and progression of type 1 or type 2 diabetes (2). Moreover, the liver is also one of the key tissues for lipid metabolism.ATP serves as an energy molecule as well as a signal molecule in many cells (3). We previously showed that leucine upregulates the ATP synthase b (ATPSb) subunit to enhance ATP synthesis and insulin secretion in rat islets, type 2 diabetic human islets, and Rattus insulin-1 (INS-1) cells. Overexpression or knockdown of ATPSb increases or reduces cellular ATP levels in INS-1 cells (4,5). Overall, these findings suggest that ATPSb plays a crucial role in controlling ATP synthesis.

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Pancreatic‐derived factor promotes lipogenesis in the mouse liver: Role of the Forkhead box 1 signaling pathway

Cited by 54 publications

References 38 publications

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

PANDER transgenic mice display fasting hyperglycemia and hepatic insulin resistance

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

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