Abstract
Background
Metabolic disorder is characterized as chronic low-grade inflammation which elevates the systemic inflammatory markers. The proposed hypothesis behind this includes occurrence of hypoxia due to intake of high fat diet leading to oxidative stress and mitochondrial dysfunction.
Aim
In the present work our aim was to elucidate the possible mechanism of action of hydroethanolic fraction of M. longifolia leaves against the metabolic disorder.
Method and results
In the present investigation, effect of Madhuca longifolia hydroethanolic fraction (MLHEF) on HFD induced obesity and diabetes through mitochondrial action and selective GLUT expression has been studied. In present work, it was observed that HFD (50% of diet) on chronic administration aggravates the metabolic problems by causing reduced imbalanced oxidative stress, ATP production, and altered selective GLUT protein expression. Long term HFD administration reduced (p < 0.001) the SOD, CAT level significantly along with elevated liver function marker AST and ALT. MLHEF administration diminishes this oxidative stress. HFD administration also causes decreased ATP/ADP ratio owing to suppressed mitochondrial function and elevating LDH level. This oxidative imbalance further leads to dysregulated GLUT expression in hepatocytes, skeletal muscles and white adipose tissue. HFD leads to significant (p < 0.001) upregulation in GLUT 1 and 3 expression while significant (p < 0.001) downregulation in GLUT 2 and 4 expressions in WAT, liver and skeletal muscles. Administration of MLHEF significantly (p < 0.001) reduced the LDH level and also reduces the mitochondrial dysfunction.
Conclusion
Imbalances in GLUT levels were significantly reversed in order to maintain GLUT expression in tissues on the administration of MLHEF.
Graphical Abstract
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Data availability
Data will be provided on request.
Abbreviations
- ATP:
-
Adenosine triphosphate
- ADP:
-
Adenosine diphosphate
- ALT:
-
Alanine transaminase
- AST:
-
Aspartate transaminase
- CAT:
-
Catalase
- FFA:
-
Free fatty acids
- GLUT:
-
Glucose transporter
- HFD:
-
High fat diet
- HIF:
-
Hypoxia inducible factor
- i.p:
-
Intraperitoneal
- IL:
-
Interleukins
- LDH:
-
Lactate dehydrogenase
- MDA:
-
Malondialdehyde
- OXPHOS:
-
Oxidative phosphorylation
- NBT:
-
Nitro blue tetrazolium
- NAD:
-
Nicotinamide adenine dinucleotide
- ROS:
-
Reactive oxygen species
- SD:
-
Standard deviation
- SDH:
-
Succinate dehydrogenase
- SOD:
-
Superoxide dismutase
- STZ:
-
Streptozotocin
- TNF:
-
Tumour necrosis factor
- WAT:
-
White adipose tissue
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Acknowledgements
The authors would like to acknowledge Ms Parul Gupta. Authors also acknowledge the Department of Pharmaceutical Sciences and Technology, BIT mesra and SAIF CDRI Lucknow for providing the facilities. Authors are grateful to UGC for providing financial assistance.
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DJ and SKP designed the study and written the manuscript. DJ, SKP, PD and MJ performed the experiment. DJ, SKP and PMM analyzed results, checked, and finalized the manuscript. The authors state that all data were generated internally and that no paper mill was used.
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Jha, D., Prajapati, S.K., Deb, P.K. et al. Madhuca longifolia-hydro-ethanolic-fraction reverses mitochondrial dysfunction and modulates selective GLUT expression in diabetic mice fed with high fat diet. Mol Biol Rep 51, 209 (2024). https://doi.org/10.1007/s11033-023-08962-9
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DOI: https://doi.org/10.1007/s11033-023-08962-9