- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06699069
Effect of Exercise on Irisin Levels of Hypothyroid Rats
The Effect of Exercise on Serum Irisin Levels in Hypothyroid Sprague Dawley Rats
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Contracting skeletal muscle acts as an endocrine organ, capable of secreting hormones called myokines, such as interleukin 1, Interleukin 15 and Irisin. Myokines are important for regulation of glucose and lipid metabolism. Among these, irisin, is an exercise induced polypeptide, secreted mainly by skeletal muscles and adipose tissue. Irisin is also secreted in small amounts from cardiac muscle, pancreas and sebaceous glands. It is cleaved and secreted from fibronectin type III domain-containing protein 5 (FNDC5 gene) and is regulated by the peroxisome proliferator-activated receptor-γ co activator 1-α (PGC1-α) .
The most important function of Irisin is thermogenesis, by inducing the browning of white adipose tissue, thereby increasing energy consumption, encouraging weight loss and decreasing dietary insulin resistance. Linking Irisin levels with obesity, its mechanism shows that after exercise there is up regulation of a thermogenin ,an Uncoupling Protein-1 (UCP-1) Thyroid hormone also plays an important role in glucose-lipid metabolism and energy homeostasis. Hypothyroidism, a decrease in thyroid hormone levels, can lead to obesity and metabolic syndrome. It has been found that thyroid hormone is also involved in thermogenesis by inducing browning of white adipose tissue, through thyroid hormone receptors. In hypothyroidism, many metabolic processes in the body are affected such as differentiation in the adipose tissue. Increased thyroid stimulating hormone (TSH) causes adipogenesis by stimulating pre-adipocyte differentiation directly through the receptors in the adipose tissue . Fatty tissue is increased by adipocyte hypertrophy as a consequence of previous adipogenesis, and newly formed adipocyte-8, resulting in clinical obesity.
FNDC5 (Fibronectin type III domain-containing protein 5), which is the precursor of irisin, is a protein that is encoded by the FNDC5 gene, is present in many tissues, including the thyroid tissue and therefore effects thyroid hormone.
Dysregulation of both Thyroid and Irisin hormones result in metabolic syndrome. The metabolic syndrome is a common metabolic disorder that has been linked to the increasing prevalence of obesity. By regulating thyroid hormone levels, irisin has a powerful impact on metabolism and thermogenesis. The association of irisin with the thyroid hormone in hypothyroidism still remains unknown and is controversial, and requires further confirmatory studies on experimental models.
Regular exercise is known to have significant beneficial effects on the metabolic health and this is mediated by skeletal muscle. Contracting skeletal muscle is the source of Irisin. Studies have shown an increase in post exercise Irisin levels
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Federal
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Islamabad, Federal, Pakistan, 44000
- National Institute Of Health
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male adult rats weighing approx. 200-250gms
- 6 to 8 week old rats
Exclusion Criteria:
- Female rats will be excluded.
- Rats with any obvious pathology
- The rats weighing >200gm
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Group I (Control or Euthyroid) total number of rats=20
Fed on normal standard diet
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Fed on normal standard diet
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Experimental: Group II (Hypothyroid) total number of rats=20
Experimental hypothyroidism will be induced by administration of propylthiouracil for three weeks in the form of tablets diluted in water
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Experimental hypothyroidism will be induced by administration of propylthiouracil for three weeks in the form of tablets diluted in water
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Experimental: Group III (Hypothyroid received exercise) total number of rats=20
Rats will be subjected to chronic swimming.
The swimming protocol will consist of 8 weeks of low-intensity swimming exercise.
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Rats will be subjected to chronic swimming.
The swimming protocol will consist of 8 weeks of low-intensity swimming exercise.
The exercise groups will be adapted to a round water tank (70 cm × 70 cm) containing water at 28 ± 2°C for 3 days (10-45 min/day).
The rats will then begin swimming, 45 min/day for the first two weeks at 10am and 60 min/day for the last six weeks at 10am
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Serum Triiodothyronine T3
Time Frame: 11th week
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Estimation of serum free triiodothyronine (FT3) levels (ng/ml) by radioimmunoassay
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11th week
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Serum Thyroxine
Time Frame: 11th week
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Estimation of serum free thyroxin (FT4) levels (μg/dl) by radioimmunoassay
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11th week
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Serum Irisin
Time Frame: 11th week
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Estimation of serum irisin levels (μg/ml) by using enzyme - linked immunosorbent assay (ELISA) using irisin competitive ELISA Kit
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11th week
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Serum Thyroid Stimulating Hormone
Time Frame: 11th week
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By radioimmunoassay
|
11th week
|
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Serum Triglycerides (TG)
Time Frame: 11th week
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By enzymatic method using micro lab analyzer
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11th week
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Serum High Density Lipoproteins (HDL)
Time Frame: 11th week
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Determined by precipitating method using micro lab analyzer
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11th week
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Serum Low Density Lipoproteins (LDL)
Time Frame: 11th week
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LDL= Total cholesterol-HDL-TG/5
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11th week
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Shazia Ali, PhD, Riphah International University
Publications and helpful links
General Publications
- Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017 Aug;11(8):215-225. doi: 10.1177/1753944717711379. Epub 2017 Jun 22.
- Martinez Munoz IY, Camarillo Romero EDS, Garduno Garcia JJ. Irisin a Novel Metabolic Biomarker: Present Knowledge and Future Directions. Int J Endocrinol. 2018 Oct 9;2018:7816806. doi: 10.1155/2018/7816806. eCollection 2018.
- Korta P, Pochec E, Mazur-Bialy A. Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases. Medicina (Kaunas). 2019 Aug 15;55(8):485. doi: 10.3390/medicina55080485.
- Gizaw M, Anandakumar P, Debela T. A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus. J Pharmacopuncture. 2017 Dec;20(4):235-242. doi: 10.3831/KPI.2017.20.029. Epub 2017 Oct 10.
- Uc ZA, Gorar S, Mizrak S, Gullu S. Irisin levels increase after treatment in patients with newly diagnosed Hashimoto thyroiditis. J Endocrinol Invest. 2019 Feb;42(2):175-181. doi: 10.1007/s40618-018-0899-8. Epub 2018 May 18.
- Maalouf GE, El Khoury D. Exercise-Induced Irisin, the Fat Browning Myokine, as a Potential Anticancer Agent. J Obes. 2019 Apr 1;2019:6561726. doi: 10.1155/2019/6561726. eCollection 2019.
- Deshmukh V, Farishta F, Bhole M. Thyroid Dysfunction in Patients with Metabolic Syndrome: A Cross-Sectional, Epidemiological, Pan-India Study. Int J Endocrinol. 2018 Dec 25;2018:2930251. doi: 10.1155/2018/2930251. eCollection 2018.
- Abdel Moety DA. Evaluation of Serum Irisin and Creatine Kinase Levels in Hypo- and Hyperthyroid Rats. Al-Azhar Med J. 2017;46(1):163-74.
- Ates I, Altay M, Topcuoglu C, Yilmaz FM. Circulating levels of irisin is elevated in hypothyroidism, a case-control study. Arch Endocrinol Metab. 2016 Apr;60(2):95-100. doi: 10.1590/2359-3997000000077. Epub 2015 Jul 21.
- Yang N, Zhang H, Gao X, Miao L, Yao Z, Xu Y, Wang G. Role of irisin in Chinese patients with hypothyroidism: an interventional study. J Int Med Res. 2019 Apr;47(4):1592-1601. doi: 10.1177/0300060518824445. Epub 2019 Feb 6.
- Teixeira PFDS, Dos Santos PB, Pazos-Moura CC. The role of thyroid hormone in metabolism and metabolic syndrome. Ther Adv Endocrinol Metab. 2020 May 13;11:2042018820917869. doi: 10.1177/2042018820917869. eCollection 2020.
- Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L, Srbecky M, Imrich R, Kyselovicova O, Belan V, Jelok I, Wolfrum C, Klimes I, Krssak M, Zemkova E, Gasperikova D, Ukropec J, Ukropcova B. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J Physiol. 2014 Mar 1;592(5):1091-107. doi: 10.1113/jphysiol.2013.264655. Epub 2013 Dec 2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRC/20/232 Fatima Iqbal
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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