Deciphering metformin action in obese mice: A critical re-evaluation of established protocols

Kaplanian, Mairam; Philippe, Cécile; Eid, Sameer Abu; Häckl, Martina; Metz, Matthäus; Beghini, Marianna; Luca, Andreea C.; Kautzky‐Willer, Alexandra; Scherer, Thomas; Fürnsinn, Clemens

doi:10.1016/j.metabol.2021.154956

Cited by 5 publications

(2 citation statements)

References 45 publications

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“…At the start of treatment (day 28), each group had initial average arthritis scores between 2.8 and 3, and 10 mg/kg metformin was injected intraperitoneally twice per week for 21 days. 46 , 47 Each paw of the saline + laser and PLGA-MET-ICG groups were exposed to an 808 nm NIR laser (650 mW) for 60s on the day after the nanoparticle injection. At the end of the experiment, the mice were euthanized, and their tissues, organs, and blood samples were collected for further study.…”

Section: Methodsmentioning

confidence: 99%

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis

Kim,

Park,

Kang

et al. 2023

IJN

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Purpose Rheumatoid arthritis (RA) is a highly prevalent form of autoimmune disease that affects nearly 1% of the global population by causing severe cartilage damage and inflammation. Despite its prevalence, previous efforts to prevent the perpetuation of RA have been hampered by therapeutics’ cytotoxicity and poor delivery to target cells. The present study exploited drug repositioning and nanotechnology to convert metformin, a widely used antidiabetic agent, into an anti-rheumatoid arthritis drug by designing poly(lactic-co-glycolic acid) (PLGA)-based spheres. Moreover, this study also explored the thermal responsiveness of the IL-22 receptor, a key regulator of Th-17, to incorporate photothermal therapy (PTT) into the nanodrug treatment. Materials and Methods PLGA nanoparticles were synthesized using the solvent evaporation method, and metformin and indocyanine green (ICG) were encapsulated in PLGA in a dropwise manner. The nanodrug’s in vitro anti-inflammatory properties were examined in J744 and FLS via real-time PCR. PTT was induced by an 808 nm near-infrared (NIR) laser, and the anti-RA effects of the nanodrug with PTT were evaluated in DBA/1 collagen-induced arthritis (CIA) mice models. Further evaluation of anti-RA properties was carried out using flow cytometry, immunofluorescence analysis, and immunohistochemical analysis. Results The encapsulation of metformin into PLGA allowed the nanodrug to enter the target cells via macropinocytosis and clathrin-mediated endocytosis. Metformin-encapsulated PLGA (PLGA-MET) demonstrated promising anti-inflammatory effects by decreasing the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), increasing the expression of anti-inflammatory cytokines (IL-10 and IL-4), and promoting the polarization of M1 to M2 macrophages in J774 cells. The treatment of the nanodrug with PTT exhibited more potent anti-inflammatory effects than free metformin or PLGA-MET in CIA mice models. Conclusion These results demonstrated that PLGA-encapsulated metformin treatment with PTT can effectively ameliorate inflammation in a spatiotemporal manner.

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Section: Methodsmentioning

confidence: 99%

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis

Kim,

Park,

Kang

et al. 2023

IJN

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show abstract

“…A large and comprehensive study has shown that weight loss benefits are related to adherence to metformin and persist for up to 10 years [ 16 ]. Recent research showed that metformin treatment inhibited body weight and fat mass gain in obese mice on a high-fat diet [ 17 , 18 ]. The American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines (2016) (2016) recommend using of metformin in individuals with obesity who have a high risk of type II diabetes or insulin intolerance and failed to respond to lifestyle interventions or anti-obesity pharmacotherapy [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells

Yang

Jia

Fang

et al. 2022

IJMS

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Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.

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MUW researcher of the month

2023

Wien Klin Wochenschr

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Deciphering metformin action in obese mice: A critical re-evaluation of established protocols

Cited by 5 publications

References 45 publications

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis

Drug Repositioning of Metformin Encapsulated in PLGA Combined with Photothermal Therapy Ameliorates Rheumatoid Arthritis

Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells

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