Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway

Awazawa, Motoharu; Ueki, Kohjiro; Inabe, Kazunori; Yamauchi, Toshimasa; Kaneko, Kazuma; Okazaki, Yukiko; Bardeesy, Nabeel; Ohnishi, S. Tsuyoshi; Nagai, Ryozo; Kadowaki, Tomoko

doi:10.1016/j.bbrc.2009.02.131

Cited by 160 publications

(115 citation statements)

References 27 publications

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“…19) Adiponectin has also been reported to down-regulate the expression of sterol regulatory element-binding protein (SREBP) 1c, the master regulator which up-regulates hepatic lipogenic enzymes, and to improve insulin sensitivity. [19][20][21] Although it is necessary to test if dietary sericin can affect the serum adiponectin concentration in a timedependent manner and influence the non-fasting plasma insulin level, our results imply that the increase in serum adiponectin by sericin intake may, at lease in part, contribute to the protective effect against hyperlipidemia, fatty liver and glucose intolerance in rats fed on a high-fat diet.…”

Section: Discussionmentioning

confidence: 78%

Consumption of Sericin Reduces Serum Lipids, Ameliorates Glucose Tolerance and Elevates Serum Adiponectin in Rats Fed a High-Fat Diet

Okazaki

Kakehi

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 78%

Consumption of Sericin Reduces Serum Lipids, Ameliorates Glucose Tolerance and Elevates Serum Adiponectin in Rats Fed a High-Fat Diet

Okazaki

Kakehi

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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“…All of the other primers and probes used were purchased from Applied Biosystems. The levels of mRNAs were normalized to that of cyclophilin (25).…”

Section: Animals Bkscg-mmentioning

confidence: 99%

“…Immunoblotting was conducted as previously described (25). The antibodies used for immunoblotting were anti-phospho-PERK antibody (Thr980; Cell Signaling Technology); anti-phosphoeukaryotic transcription initiation factor 2 alpha subunit (anti-phosphoeIF2␣) antibody (Ser51; Cell Signaling Technology); anti-4E-BP1 antibody (Cell Signaling), and anti-␤-actin antibody (Sigma-Aldrich).…”

Section: Animals Bkscg-mmentioning

confidence: 99%

Deregulation of Pancreas-Specific Oxidoreductin ERO1β in the Pathogenesis of Diabetes Mellitus

Awazawa

Futami

Sakada

et al. 2014

Molecular and Cellular Biology

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A growing body of evidence has underlined the significance of endoplasmic reticulum (ER) stress in the pathogenesis of diabetes mellitus. ER oxidoreductin 1␤ (ERO1␤) is a pancreas-specific disulfide oxidase that is known to be upregulated in response to ER stress and to promote protein folding in pancreatic ␤ cells. It has recently been demonstrated that ERO1␤ promotes insulin biogenesis in ␤ cells and thus contributes to physiological glucose homeostasis, though it is unknown if ERO1␤ is involved in the pathogenesis of diabetes mellitus. Here we show that in diabetic model mice, ERO1␤ expression is paradoxically decreased in ␤ cells despite the indications of increased ER stress. However, overexpression of ERO1␤ in ␤ cells led to the upregulation of unfolded protein response genes and markedly enlarged ER lumens, indicating that ERO1␤ overexpression caused ER stress in the ␤ cells. Insulin contents were decreased in the ␤ cells that overexpressed ERO1␤, leading to impaired insulin secretion in response to glucose stimulation. These data indicate the importance of the fine-tuning of the ER redox state, the disturbance of which would compromise the function of ␤ cells in insulin synthesis and thus contribute to the pathogenesis of diabetes mellitus.

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“…More-over, AMPK and its activating kinase LKB1 are required for adiponectin to reduce the expression of the lipogenic gene Srebf1c (28). While these studies suggest that some effects of adiponectin depend on AMPK, it is unclear whether this pathway accounts for all the actions of this adipokine.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling

Miller¹,

Chu²,

Lay³

et al. 2011

J. Clin. Invest.

155

102

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The adipocyte-derived hormone adiponectin signals from the fat storage depot to regulate metabolism in peripheral tissues. Inversely correlated with body fat levels, adiponectin reduction in obese individuals may play a causal role in the symptoms of metabolic syndrome. Adiponectin lowers serum glucose through suppression of hepatic glucose production, an effect attributed to activation of AMPK. Here, we investigated the signaling pathways that mediate the effects of adiponectin by studying mice with inducible hepatic deletion of LKB1, an upstream regulator of AMPK. We found that loss of LKB1 in the liver partially impaired the ability of adiponectin to lower serum glucose, though other actions of the hormone were preserved, including reduction of gluconeogenic gene expression and hepatic glucose production as assessed by euglycemic hyperinsulinemic clamp. Furthermore, in primary mouse hepatocytes, the absence of LKB1, AMPK, or the transcriptional coactivator CRTC2 did not prevent adiponectin from inhibiting glucose output or reducing gluconeogenic gene expression. These results reveal that whereas some of the hormone's actions in vivo may be LKB1 dependent, substantial LKB1-, AMPK-, and CRTC2-independent signaling pathways also mediate effects of adiponectin.

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Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway

Cited by 160 publications

References 27 publications

Consumption of Sericin Reduces Serum Lipids, Ameliorates Glucose Tolerance and Elevates Serum Adiponectin in Rats Fed a High-Fat Diet

Consumption of Sericin Reduces Serum Lipids, Ameliorates Glucose Tolerance and Elevates Serum Adiponectin in Rats Fed a High-Fat Diet

Deregulation of Pancreas-Specific Oxidoreductin ERO1β in the Pathogenesis of Diabetes Mellitus

Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling

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