Canagliflozin ameliorates hepatic fat deposition in obese diabetic mice: Role of prostaglandin E2

Yoshino, Kei; Hosooka, Tetsuya; Shinohara, Masakazu; Aoki, Chikako; Hosokawa, Yusei; Imamori, Makoto; Ogawa, Wataru

doi:10.1016/j.bbrc.2021.04.012

Cited by 12 publications

(12 citation statements)

References 23 publications

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“…Mouse primary hepatocytes were isolated from male C57BL/6J mice (CLEA Japan) by enzymatic digestion with collagenase essentially as described 41 – 43 . The isolated hepatocytes were seeded at a density of 2.25 × 10 5 cells per well in 6-well plates (coated with collagen) for immunoblot in William's E Medium with 5% FBS 0.5%, penicillin, and 0.5% streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes

Hozumi

Sugawara

Ishihara

et al. 2023

Sci Rep

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Imeglimin is a recently launched antidiabetic drug structurally related to metformin. To provide insight into the pharmacological properties of imeglimin, we investigated its effects on hepatocytes and compared them with those of metformin. The effects of imeglimin on mitochondrial function in HepG2 cells or mouse primary hepatocytes were examined with an extracellular flux analyzer and on gene expression in HepG2 cells by comprehensive RNA-sequencing analysis. The effects of the drug on AMPK activity in HepG2 cells, mouse primary hepatocytes, and mouse liver were also examined. Treatment of HepG2 cells or mouse primary hepatocytes with imeglimin reduced the oxygen consumption rate coupled to ATP production. Imeglimin activated AMPK in these cells whereas the potency was smaller than metformin. Bolus administration of imeglimin in mice also activated AMPK in the liver. Whereas the effects of imeglimin and metformin on gene expression in HepG2 cells were similar overall, the expression of genes encoding proteins of mitochondrial respiratory complex III and complex I was upregulated by imeglimin but not by metformin. Our results suggest that imeglimin and metformin exert similar pharmacological effects on mitochondrial respiration, AMPK activity, and gene expression in cultured hepatocytes, whereas the two drugs differ in their effects on the expression of certain genes related to mitochondrial function.

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Section: Methodsmentioning

confidence: 99%

Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes

Hozumi

Sugawara

Ishihara

et al. 2023

Sci Rep

Self Cite

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“…In obstructive sleep apnea patients, a five-lipid group comprising 25-cinnamoyl-vulgaroside, glycocholic acid, bilirubin, and two previously unreported lipid species changed significantly after continuous positive airway pressure treatment [60]. Canagliflozin treatment increased the amounts of prostaglandin E2 and resolvin E3 in the liver of obese mice used as a biological model to understand the NAFLD [97]. Saroglitazar, a PPAR α/γ agonist, protected patients against obesity, insulin resistance, and steatosis by reducing TG and modulating phospholipid levels.…”

Section: Human β-Hexosaminidase A) Human β-Hexosaminidase Isoenzyme A...mentioning

confidence: 99%

Lipidomics as a Tool in the Diagnosis and Clinical Therapy

Sánchez¹,

Ontiveros²,

Arreola³

et al. 2023

Fatty Acids - From Biosynthesis to Human Health

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The lipids are essential compounds of cells, with biochemical and structural properties. Lipids are classified according to their chain length or saturation levels and biogenesis. Lipidomics is a spectroscopic and spectrometric technique, like Mass Spectrometry and Nuclear Magnetic Resonance, as well as bioinformatics to quantify and characterize the lipid profile. Lipidomics enables the fundamental understanding of lipid biology, the identification of drug targets for therapy, and the discovery of lipid biomarkers of disease cohorts. Therefore, lipidomics allows knowing the diagnosis and clinical follow-up in medical therapy towards any disease. In this way, the lipid profile allows us to monitor the administration of a clinical treatment and assertively diagnose human diseases.

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“…However, it should be noted that not all studies point towards a beneficial effect of SGLT-2i on body weight. Several studies have shown that administration of SGLT-2i does not exert any significant effect on body weight gain, epididymal fat weight or food intake [ 30 , 105 , 110 , 111 ]. In addition, although several studies reported strong effects of low dose ipragliflozin ( Table 4 ) on weight loss [ 100 , 112 , 113 ], supplementation of an AMLN diet with 40 mg ipragliflozin/kg for 8 weeks did not significantly alter the body weight of AMLN diet fed mice, while it improved liver function, hepatic fibrosis and NA score [ 114 ].…”

Section: Sglt-2 Inhibitors In Nafldmentioning

confidence: 99%

“…Although there are studies showing that administration of SGLT-2i does not exert any significant effect on body weight gain [ 30 , 100 , 110 , 111 , 112 , 113 , 114 ], the vast majority of the literature points towards a beneficial effect on weight loss.…”

Section: Sglt-2 Inhibitors In Nafldmentioning

confidence: 99%

“…Administration of canagliflozin at doses of 10 and 20 mg/kg/day ameliorated the HFD-induced down-regulation of the expression of the key regulatory molecule of hepatic lipolysis, known as zinc alpha 2 glycoprotein (ZAG). When the same SGLT-2i was given in KK-Ay mice, it reduced the accumulation of lipid droplets in the liver by increasing hepatic prostaglandin E2 (PGE2) protein levels [ 111 ]. Furthermore, the combined therapy with canagliflozin and exercise exerted an additive effect on hepatic PPARγ Coactivator 1 Beta (PGC1b) elevation, and reduced expression of hepatic lipogenic genes, such as Scd1 [ 108 ].…”

Section: Sglt-2 Inhibitors In Nafldmentioning

confidence: 99%

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SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

Ανδρουτσάκος

Nasiri-Ansari

Bakasis

et al. 2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.

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Canagliflozin ameliorates hepatic fat deposition in obese diabetic mice: Role of prostaglandin E2

Cited by 12 publications

References 23 publications

Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes

Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes

Lipidomics as a Tool in the Diagnosis and Clinical Therapy

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

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