Abstract
The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum. Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly (p < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment—insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly (p < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein—α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance.
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Abbreviations
- AMPK:
-
Adenosine monophosphate activated protein kinase
- ACC:
-
Acetyl-CoA carboxylase
- AST:
-
Aspartate transaminase
- ALT:
-
Alanine transaminase
- CVDs:
-
Cardiovascular diseases
- FAS:
-
Fatty acid synthase
- HFD:
-
High-fat diet
- HOMA-IR:
-
Homeostasis model assessment-insulin resistance
- ITT:
-
Insulin tolerance test
- IRS-1:
-
Insulin receptor substrate-1
- LPL:
-
Lipoprotein lipase
- OGTT:
-
Oral glucose tolerance test
- SREBP-1c:
-
Sterol regulatory element-binding proteins-1c
- ThyQ:
-
Thymoquinone
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Acknowledgements
The authors are grateful to the DST-FIST, Department of Biochemistry, Sri Venkateswara University, Tirupati.
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The concept was devised and developed by BM. DPR and RG performed characterization of ThyQ and N. sativa seeds fraction by using LC-HRMS and GC–MS analysis. Animal experiments were carried out by KRS, KR, and VM. KRS, SG and BM gathered and wrote the information, as well as did statistical analysis. RSK and MB performed data analysis and/or interpretation. Data paraphrasing and corrections were done by SIM. The manuscript was written, edited, and formatted by KR, RSK and MB.
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Ramineedu, K., Sankaran, K.R., Mallepogu, V. et al. Thymoquinone mitigates obesity and diabetic parameters through regulation of major adipokines, key lipid metabolizing enzymes and AMPK/p-AMPK in diet-induced obese rats. 3 Biotech 14, 16 (2024). https://doi.org/10.1007/s13205-023-03847-x
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DOI: https://doi.org/10.1007/s13205-023-03847-x