AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice

Carneiro, Lionel; Asrih, Mohamed; Repond, Cendrine; Sempoux, Christine; Stehle, Jean-Christophe; Leloup, Corinne; Jornayvaz, François R.; Pellerin, Luc

doi:10.1016/j.molmet.2017.10.005

Cited by 35 publications

(38 citation statements)

References 30 publications

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“…injection), control of glycemia at 0, 15, 30, 45, 60, and 120 min after injection. [47,48] Alanine and glutamine tolerance tests Glutamine and alanine are two major amino acids transported from the muscles during periods of active gluconeogenesis. Therefore.…”

Section: Discussionmentioning

confidence: 99%

<p>Guidelines and Considerations for Metabolic Tolerance Tests in Mice</p>

Benedé-Ubieto¹,

Estévez-Vázquez²,

Ramadori³

et al. 2020

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The epidemic of the century, Diabetes Mellitus (DM) is continuously rising. Intensive research is urgently needed whereby experimental models represent an essential tool to optimise the diagnostic strategy and to improve therapy. In this review, we describe the central principles of the metabolic tests available in order to study glucose and insulin homeostasis in mice, focusing on the most widely usedthe glucose and insulin tolerance tests. We provide detailed experimental procedures as well as the practical implementation of these methods and discuss the main factors that should be taken into account when using this methodology.

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Section: Discussionmentioning

confidence: 99%

<p>Guidelines and Considerations for Metabolic Tolerance Tests in Mice</p>

Benedé-Ubieto¹,

Estévez-Vázquez²,

Ramadori³

et al. 2020

DMSO

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“…Its activation in the liver favors energy producing and not energy consuming processes such as fatty acid synthesis (Carneiro et al. ). This downregulation of energy consuming processes is achieved through the inhibition of the sterol regulatory element binding protein 1 (SREBP1) and consequently repressing key transcription factors such as peroxisome proliferator‐activated receptors (PPAR) that are involved in lipid metabolism (Carneiro et al.…”

Section: Introductionmentioning

confidence: 99%

“…This downregulation of energy consuming processes is achieved through the inhibition of the sterol regulatory element binding protein 1 (SREBP1) and consequently repressing key transcription factors such as peroxisome proliferator‐activated receptors (PPAR) that are involved in lipid metabolism (Carneiro et al. ). It is important, however, to note that while the upregulation of AMPK protects against hepatic steatosis, its downregulation does not indicate susceptibility to hepatic steatosis (Boudaba et al.…”

Section: Introductionmentioning

confidence: 99%

The long‐term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high‐fructose‐fed adolescent rats

et al. 2019

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There is an increased prevalence of nonalcoholic steatohepatitis ( NASH ) in adolescents. The suckling period is developmentally plastic, affecting later health outcomes. We investigated whether neonatal administration of curcumin would provide protection against the development of NASH later in adolescence in rats fed a high‐fructose diet. From postnatal day ( PN ) 6 to PN 21, the pups ( N = 128) were allocated to four groups and orally gavaged daily with either 0.5% dimethyl sulfoxide solution (vehicle control), curcumin (500 mg·kg −1 ), fructose (20%, w/v) or curcumin and fructose combined. All the pups were weaned and half the rats in each group had tap water, whereas the other received fructose (20%) as their drinking fluid ad libitum for 6 weeks. The rats’ liver NASH scores, lipid content, and RNA gene expression ratios of AMPK α and TNF α were determined. Hepatic lipid content was similar across the treatment groups in the males ( P > 0.05, ANOVA ). In the females, the hepatic lipid content in the treatment groups ranged from 2.7 to 4.3%. The livers of male and female rats that had fructose either as neonates and/or postweaning had significantly marked inflammation ( P = 0.0112, Kruskal–Wallis) and fibrosis ( P < 0.0001, ANOVA ) which were attenuated by curcumin. The hepatic gene expression ratios for AMPK α in both sexes were significantly downregulated ( P < 0.0001, ANOVA ), whereas the expression ratios of TNF α were significantly upregulated ( P < 0.0001) in rats fed a high‐fructose diet pre and/or postweaning compared to the other groups. Neonatal curcumin administration is a potential natural pharmacological candidate for the prevention of NASH .

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“…Adenosine monophosphate‐activated protein kinase (AMPK) is a crucial cellular energy sensor that is activated by changes in physiological conditions mediated by metabolic hormones, different cell stress conditions, and also pharmacological molecules (Carling, ; Hardie, Schaffer, & Brunet, ). Once activated, AMPK promotes changes in energy levels (Hardie, Ross, & Hawley, ; Qiu et al, ), or a shift in glucose metabolism toward lactate metabolism in tumors and MCT1+/− mice (Carneiro et al, ; Faubert et al, ; Lage, Dieguez, Vidal‐Puig, & Lopez, ). Furthermore, our recent study suggested that AMPK acts as a negative regulator of hyperthermia‐induced lactate secretion by decreasing the expression levels of GLUT3 , LDHA , and MCT1 in cultured boar SCs (Yu et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…physiological conditions mediated by metabolic hormones, different cell stress conditions, and also pharmacological molecules (Carling, 2017;Hardie, Schaffer, & Brunet, 2016). Once activated, AMPK promotes changes in energy levels (Hardie, Ross, & Hawley, 2012;Qiu et al, 2018), or a shift in glucose metabolism toward lactate metabolism in tumors and MCT1+/− mice (Carneiro et al, 2017;Faubert et al, 2013;Lage, Dieguez, Vidal-Puig, & Lopez, 2008).…”

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confidence: 99%

MiR‐8‐3p regulates hyperthermia‐induced lactate secretion by targeting PPP2R5B in boar Sertoli cells

Deng

Tian

et al. 2019

Molecular Reproduction Devel

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Lactate produced by glycolysis in Sertoli cells (SCs) is the main energy substrate for developing germ cells and plays a vital role in spermatogenesis. MicroRNAs (miRNAs) function as posttranscriptional regulators of gene expression in biological processes. We have previously shown that hyperthermia (43°C, 30 min) promotes lactate secretion by inhibiting phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK) in cultured immature boar SCs. However, it is unclear whether miRNAs are involved in AMPK‐modulated glycolysis in SCs. In the present study, we identified 349 miRNAs (227 upregulated and 122 downregulated) in hyperthermia‐treated boar SCs by next‐generation high‐throughput RNA sequencing. MiR‐8‐3p, which was found to be a novel upregulated miRNA in hyperthermia‐treated SCs, suppressed the expression of AMPK upstream genes (protein phosphatase 2 subunit B, PPP2R5B), and further downregulated the expression of p‐AMPK. The miR‐8‐3p mimic upregulated expression of glucose transporter 3, lactate dehydrogenase A and monocarboxylate transporter 1, and increased lactic acid dehydrogenase activity, lactate secretion, and ATP depletion in SCs; the miR‐8‐3p inhibitor had the opposite effects on these parameters. Our findings indicate that miR‐8‐3p acts as a novel regulator of AMPK‐modulated lactate secretion by targeting PPP2R5B in hyperthermic boar SCs.

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AMPK activation caused by reduced liver lactate metabolism protects against hepatic steatosis in MCT1 haploinsufficient mice

Cited by 35 publications

References 30 publications

<p>Guidelines and Considerations for Metabolic Tolerance Tests in Mice</p>

<p>Guidelines and Considerations for Metabolic Tolerance Tests in Mice</p>

The long‐term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high‐fructose‐fed adolescent rats

MiR‐8‐3p regulates hyperthermia‐induced lactate secretion by targeting PPP2R5B in boar Sertoli cells

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