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Published on: April 16, 2019
Thyroidectomy stimulates glucagon-like peptide-1 secretion and attenuates hepatic steatosis in high-fat fed rats
Jong Yeon Kang1, Mikyung Kim1, Yuna Kang2
1Department of Biochemistry, School of Medicine, Keimyung University, Daegu, Republic of Korea.
Abstract:
Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low-density lipoprotein in HN Thx. Unexpectedly, however, Thx reduced serum and hepatic triglyceride concentrations. Further studies revealed that Thx dramatically increased circulating GLP-1 as well as increased expressions of GLP-1 in small intestine. Diminished hepatic expressions of lipogenic genes, were observed in HN Thx group. Beta-catenin and glutamine synthetase, a known target of β-catenin, were up-regulated in the liver of HN Thx group. The expressions of gluconeogenic genes G6P and PCK were reduced in the liver of HN Thx group. The results may suggest that surgery-induced hypothyroidism increases GLP-1, the actions of which may in part be responsible for the reduction in water intake, appetite and hepatic steatosis.
Insights
Surgery-induced hypothyroidism in rats reduced body weight and appetite. This metabolic shift was linked to increased GLP-1, suggesting a potential therapeutic pathway for obesity and fatty liver disease.
Area of Science:
- Metabolic research
- Endocrinology
- Obesity research
Background:
- Thyroid hormones (THs) influence metabolism, but their precise role in obesity treatment remains unclear.
- Understanding the mechanisms of TH action is crucial for developing effective obesity interventions.
Purpose of the Study:
- To investigate the metabolic effects of surgically induced hypothyroidism in high-fat diet (HFD) fed rats.
- To elucidate the detailed mechanisms underlying these metabolic changes.
Main Methods:
- Surgical thyroidectomy (Thx) was performed on HFD-fed Sprague Dawley (SD) rats.
- Evaluated body weight, food and water intake, insulin response, lipid profiles, and gene expression.
- Measured circulating and intestinal glucagon-like peptide-1 (GLP-1) levels.
Main Results:
- Hypothyroid rats exhibited decreased body weight, food, and water intake.
- Total cholesterol, HDL, and LDL increased, while serum and hepatic triglycerides decreased.
- Circulating and small intestine GLP-1 expression significantly increased.
- Hepatic expression of lipogenic genes decreased, while beta-catenin and glutamine synthetase were upregulated.
- Gluconeogenic genes (G6P, PCK) expression in the liver was reduced.
Conclusions:
- Surgery-induced hypothyroidism in HFD rats leads to reduced appetite and body weight.
- Increased GLP-1 appears to play a role in mediating these effects, potentially reducing hepatic steatosis.
- These findings suggest hypothyroidism's impact on metabolic regulation and offer insights into potential therapeutic strategies for obesity.
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