Metformin prevents <i>LYRM1</i>-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism

Qin, Zhen-Ying; Zhang, Min; Dai, Yongmei; Wang, Yumei; Zhu, Guan-zhong; Zhao, Yaping; Ji, Chenbo; Qiu, Jie; Cao, Xiangyu; Guo, Xirong

doi:10.1177/1535370214537746

Cited by 14 publications

(7 citation statements)

References 42 publications

(139 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the supply of lipoic acid had a positive effect on insulin-dependent signaling in L6 myotubes [ 72 ] and ameliorated the negative effects induced by LYRM1 overexpression [ 73 ]. A similar outcome was observed for the anti-diabetic drug, Metformin [ 74 ], which is also an inhibitor of respiratory complex I [ 75 ]. Overall, these results suggest that LYRM1 takes part in a metabolic redox-dependent signaling pathway connected to mitochondrial biogenesis and homeostasis (PI3K, Akt/PKB pathway).…”

Section: The Diverse Roles Of the Lyr Motif Proteins In Mitochondrsupporting

confidence: 73%

Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes

Angerer

2015

Biology

View full text Add to dashboard Cite

In eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways. LYR (leucine/tyrosine/arginine) motif proteins (LYRMs) of the Complex1_LYR-like superfamily interact with protein complexes of bacterial origin. Many LYR proteins function as extra subunits (LYRM3 and LYRM6) or novel assembly factors (LYRM7, LYRM8, ACN9 and FMC1) of the oxidative phosphorylation (OXPHOS) core complexes. Structural insights into complex I accessory subunits LYRM6 and LYRM3 have been provided by analyses of EM and X-ray structures of complex I from bovine and the yeast Yarrowia lipolytica, respectively. Combined structural and biochemical studies revealed that LYRM6 resides at the matrix arm close to the ubiquinone reduction site. For LYRM3, a position at the distal proton-pumping membrane arm facing the matrix space is suggested. Both LYRMs are supposed to anchor an acyl-carrier protein (ACPM) independently to complex I. The function of this duplicated protein interaction of ACPM with respiratory complex I is still unknown. Analysis of protein-protein interaction screens, genetic analyses and predicted multi-domain LYRMs offer further clues on an interaction network and adaptor-like function of LYR proteins in mitochondria.

show abstract

Section: The Diverse Roles Of the Lyr Motif Proteins In Mitochondrsupporting

confidence: 73%

Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes

Angerer

2015

Biology

View full text Add to dashboard Cite

show abstract

“…Exercise-induced PGC1α plays a crucial role in the regulation of muscle metabolism and stimulates the release of METRNL from skeletal muscle 6 . AMPK stimulates PGC1α-mediated signaling 18 , 19 . PGC1α has previously been shown to exhibit powerful suppressive effects on inflammation 20 and insulin resistance 21 .…”

Section: Resultsmentioning

confidence: 99%

METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice

et al. 2018

View full text Add to dashboard Cite

Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1). METRNL treatment also attenuated the impaired insulin response both in palmitate-treated differentiated C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore, METRNL administration rescued glucose intolerance and reduced HFD-induced body weight gain in mice; however, METRNL did not affect calorie intake. METRNL treatment increased AMPK phosphorylation and PPARδ expression both in differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression of AMPK and PPARδ abrogated the suppressive effects of METRNL on palmitate-induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA expression of fatty acid oxidation-associated genes, such as carnitine palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding protein 3 (FABP3). siRNAs for AMPK and PPARδ reversed these changes. In the current study, we report for the first time that METRNL alleviates inflammation and insulin resistance and induces fatty acid oxidation through AMPK or PPARδ-dependent signaling in skeletal muscle.

show abstract

“…35 Studies have shown that drugs such as resveratrol, metformin and tetramethylpyrazine all target SIRT1 to increase mitochondrial biogenesis through PGC-1α-dependent pathways. [36][37][38] Further investigations by Ham PB and Price NL have revealed the essential role of resveratrol in mediating AMPK to stimulate SITR1 and induce mitochondrial biogenesis. Resveratrol could increase the activities of cAMP, AMPK and NAD + .…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1‐mediated mitochondrial biogenesis plays an important role in disease progression 35 . Studies have shown that drugs such as resveratrol, metformin and tetramethylpyrazine all target SIRT1 to increase mitochondrial biogenesis through PGC‐1α‐dependent pathways 36–38 . Further investigations by Ham PB and Price NL have revealed the essential role of resveratrol in mediating AMPK to stimulate SITR1 and induce mitochondrial biogenesis.…”

Section: Discussionmentioning

confidence: 99%

BMAL1 regulates mitochondrial homeostasis in renal ischaemia‐reperfusion injury by mediating the SIRT1/PGC‐1α axis

Huang

et al. 2022

J Cellular Molecular Medi

View full text Add to dashboard Cite

The regulation of renal function by circadian gene BMAL1 has been recently recognized; however, the role and mechanism of BMAL1 in renal ischaemia-reperfusion injury (IRI) are still unknown. The purpose of this study was to clarify the pathophysiological role of BMAL1 in renal IRI. We measured the levels of BMAL1 and mitochondrial biogenesis-related proteins, including SIRT1, PGC-1α, NRF1 and TFAM, in rats with renal IRI. In rats, the level of BMAL1 decreased significantly, resulting in inhibition of SIRT1 expression and mitochondrial biogenesis. In addition, under hypoxia and reoxygenation (H/R) stimulation, BMAL1 knockdown decreased the level of SIRT1 and exacerbated the degree of mitochondrial damage and apoptosis.Overexpression of BMAL1 alleviated H/R-induced injury. Furthermore, application of the SIRT1 inhibitor EX527 not only reduced the activities of SIRT1 and PGC-1α but also further aggravated mitochondrial dysfunction and partially reversed the protective effect of BMAL1 overexpression. Moreover, whether in vivo or in vitro, the application of SIRT1 agonist resveratrol rescued the mitochondrial dysfunction caused by H/R or IRI by activating mitochondrial biogenesis. These results indicate that BMAL1 is a key circadian gene that mediates mitochondrial homeostasis in renal IRI through the SIRT1/PGC-1α axis, which provides a new direction for targeted therapy for renal IRI.

show abstract

Metformin prevents LYRM1-induced insulin resistance in 3T3-L1 adipocytes via a mitochondrial-dependent mechanism

Cited by 14 publications

References 42 publications

Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes

Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes

METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice

BMAL1 regulates mitochondrial homeostasis in renal ischaemia‐reperfusion injury by mediating the SIRT1/PGC‐1α axis

Contact Info

Product

Resources

About