Inhibition of Mitochondrial Fission by Drp-1 Blockade Improves White Adipose Tissue Abnormalities in Obesity and Diabetes Article Swipe
Paola Finocchietto
,
Hernán Pérez
,
Guillermo Blanco
,
Ver nica Miksztowicz
,
Clarisa Marotte
,
Celina Morales
,
Jorge G. Peralta
,
Gabriela Berg
,
Cecilia Poderoso
,
Juan José Poderoso
,
Marı́a Cecilia Carreras
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.22541/au.159586069.98939770
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.22541/au.159586069.98939770
Background and Purpose: Obesity and Type 2 Diabetes are major causes of morbidity-mortality characterized by mitochondrial dysfunction and oxidative-nitrosative stress. Despite intensive research, the events that cause the onset and progression of these diseases are not completely understood. Herein, we investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. Experimental Approach: Mitochondrial dynamics and biogenesis were evaluated in epididymal white adipose tissue and adipocytes from ob/ob mice, an animal model of obesity and diabetes, pharmacological treatment with mdvi-1, a selective inhibitor of Drp1 and leptin. Key Results: A decrease of Mfn2 and OPA-1 protein expression and an increase in Drp1- protein levels were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals. The content of mitochondrial DNA and mRNA expression of PGC-1α, both parameters of mitochondrial biogenesis, were reduced in ob/ob mice. The treatment with leptin or mdvi-1 (Drp1 inhibitor) significantly increased abnormal biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, and adipogenesis, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdvi-1 increase substrates oxidation while in vivo determination of blood glucose showed decreased blood glucose concentration by 50 % in ob/ob mice, almost to the wt level. Conclusion and Implications: In light of these results, pharmacological targeting of Drp1 may be a potential novel therapeutic tool for obesity and diabetes.
Related Topics
Concepts
Mitochondrial biogenesis
MFN2
Internal medicine
Endocrinology
FIS1
mitochondrial fusion
Leptin
Mitochondrial fission
Adipose tissue
White adipose tissue
Mitochondrion
Biology
Type 2 diabetes
Adiponectin
Adipogenesis
Diabetes mellitus
Mitochondrial DNA
Medicine
Obesity
Insulin resistance
Cell biology
Biochemistry
Gene
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.22541/au.159586069.98939770
- https://www.authorea.com/doi/pdf/10.22541/au.159586069.98939770
- OA Status
- gold
- References
- 44
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4214575800
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4214575800Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.22541/au.159586069.98939770Digital Object Identifier
- Title
-
Inhibition of Mitochondrial Fission by Drp-1 Blockade Improves White Adipose Tissue Abnormalities in Obesity and DiabetesWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-07-27Full publication date if available
- Authors
-
Paola Finocchietto, Hernán Pérez, Guillermo Blanco, Ver nica Miksztowicz, Clarisa Marotte, Celina Morales, Jorge G. Peralta, Gabriela Berg, Cecilia Poderoso, Juan José Poderoso, Marı́a Cecilia CarrerasList of authors in order
- Landing page
-
https://doi.org/10.22541/au.159586069.98939770Publisher landing page
- PDF URL
-
https://www.authorea.com/doi/pdf/10.22541/au.159586069.98939770Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.authorea.com/doi/pdf/10.22541/au.159586069.98939770Direct OA link when available
- Concepts
-
Mitochondrial biogenesis, MFN2, Internal medicine, Endocrinology, FIS1, mitochondrial fusion, Leptin, Mitochondrial fission, Adipose tissue, White adipose tissue, Mitochondrion, Biology, Type 2 diabetes, Adiponectin, Adipogenesis, Diabetes mellitus, Mitochondrial DNA, Medicine, Obesity, Insulin resistance, Cell biology, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
44Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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