Role of Melatonin in obesity and its associated inflammation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Role of Melatonin in obesity and its associated
inflammation
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| Creator |
Saha, Moumita
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
Obesity is a chronic metabolic imbalance between consumed and expended calories acting as
an autonomous risk factor for the onset and development of T2DM, CKD, CVD and NAFLD.
Hepatic steatosis affects approx. 70–80% of people with obesity and non-alcoholic
steatohepatitis affects 15–30% of them. Melatonin (MLT), the pineal hormone, is one of the
mostly studied hormones with strong antioxidant and anti-inflammatory properties. There are
reports on protective role of MLT over obesity and obesity associated liver diseases including
NAFLD and NASH, however the detailed mechanism is not yet fully explored. Hence, the
present study investigated the role of MLT in improvement of NAFLD and NASH in murine
and cellular model. The result demonstrated that MLT administration reduced HFD (High fat
diet) induced steatotic and non-alcoholic steatohepatitic indices, which successively restored
the hepatic morphological architecture and other pathophysiological features. The results
indicated that MLT administration caused the recovery from both FFA and HFD induced
ferroptotic state via increasing GSH and SOD level, decreasing lipid ROS and MDA level,
increasing Nrf2 and HO-1 level to defend cells against an oxidative environment. MLT also
altered the expression of two key proteins GPX4 and SLC7A11 back to their normal levels,
which would otherwise cause ferroptosis. Our data suggests MLT also had control over
pAMPKα, SREBP1c, FAS, PPARγ and PPARα to reduce lipogenesis and cellular lipid
homeostasis. Furthermore, the application of MLT suppressed HFD-induced activation of the
inflammasome and through TLR4/NF-κB signaling. Here we also report that MLT
significantly suppresses P2X7R expression and calcium influx along with inflammasome
(NLRP3, ASC and Caspase 1) in both in vitro and in vivo NASH model. This study reflects
that MLT could be used as a therapeutic agent in the high-fat diet-induced NAFLD and NASH
model as it has persuasive anti-oxidant and anti-inflammatory potential.
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| Date |
2022
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2856/1/Moumita_Saha_thesis.pdf
Saha, Moumita (2022) Role of Melatonin in obesity and its associated inflammation. PhD thesis, UNIVERSITY OF CALCUTTA. |
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| Relation |
http://www.eprints.iicb.res.in/2856/
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