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Updated: May 19, 2026
Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)
Published on: January 7, 2018
Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice
Young-Sil Lee1, Byung-Yoon Cha, Sun-Sil Choi
1Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan.
Abstract:
Nobiletin (NOB) is a polymethoxylated flavone present in citrus fruits and has been reported to have antitumor and anti-inflammatory effects. However, little is known about the effects of NOB on obesity and insulin resistance. In this study, we examined the effects of NOB on obesity and insulin resistance, and the underlying mechanisms, in high-fat diet (HFD)-induced obese mice. Obese mice were fed a HFD for 8 weeks and then treated without (HFD control group) or with NOB at 10 or 100mg/kg. NOB decreased body weight gain, white adipose tissue (WAT) weight and plasma triglyceride. Plasma glucose levels tended to decrease compared with the HFD group and improved plasma adiponectin levels and glucose tolerance. Furthermore, NOB altered the expression levels of several lipid metabolism-related and adipokine genes. NOB increased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, PPAR-α, carnitine palmitoyltransferase-1, uncoupling protein-2 and adiponectin, and decreased the mRNA expression of tumor necrosis factor-α and monocyte chemoattractant protein-1 in WAT. NOB also up-regulated glucose transporter-4 protein expression and Akt phosphorylation and suppressed IκBα degradation in WAT. Taken together, these results suggest that NOB improves adiposity, dyslipidemia, hyperglycemia and insulin resistance. These effects may be elicited by regulating the expression of lipid metabolism-related and adipokine genes, and by regulating the expression of inflammatory makers and activity of the insulin signaling pathway.
Insights
Nobiletin (NOB), a citrus flavone, effectively combats obesity and insulin resistance in mice by regulating lipid metabolism, inflammation, and insulin signaling pathways. This natural compound offers a promising therapeutic avenue for metabolic disorders.
Area of Science:
- Biochemistry
- Metabolic Research
- Pharmacology
Background:
- Nobiletin (NOB), a polymethoxylated flavone from citrus fruits, exhibits known antitumor and anti-inflammatory properties.
- The specific effects of NOB on obesity and insulin resistance remain largely unexplored.
- Understanding NOB's impact on metabolic health is crucial given the rising prevalence of obesity and related disorders.
Purpose of the Study:
- To investigate the effects of NOB on obesity and insulin resistance in a high-fat diet (HFD)-induced mouse model.
- To elucidate the underlying molecular mechanisms by which NOB exerts its metabolic benefits.
- To evaluate NOB's potential as a therapeutic agent for metabolic dysfunction.
Main Methods:
- Induction of obesity in mice using an 8-week high-fat diet (HFD).
- Administration of NOB (10 or 100 mg/kg) to HFD-fed mice.
- Analysis of body weight, white adipose tissue (WAT) weight, plasma triglyceride, glucose levels, and glucose tolerance.
- Gene expression analysis of lipid metabolism and adipokine markers in WAT.
- Assessment of glucose transporter-4 (GLUT4) protein expression, Akt phosphorylation, and IκBα degradation in WAT.
Main Results:
- NOB significantly reduced body weight gain, WAT weight, and plasma triglyceride levels.
- NOB treatment led to a tendency for decreased plasma glucose and improved glucose tolerance and adiponectin levels.
- NOB modulated the expression of key genes involved in lipid metabolism (e.g., PPAR-γ, SREBP-1c, CPT1) and inflammation (e.g., TNF-α, MCP-1).
- NOB upregulated GLUT4 protein expression and Akt phosphorylation while suppressing IκBα degradation in WAT, indicating enhanced insulin signaling.
Conclusions:
- NOB effectively ameliorates obesity, dyslipidemia, hyperglycemia, and insulin resistance in HFD-induced obese mice.
- The beneficial effects of NOB are attributed to the regulation of lipid metabolism-related genes, adipokines, inflammatory markers, and the insulin signaling pathway.
- Nobiletin demonstrates significant potential as a natural compound for managing metabolic disorders like obesity and insulin resistance.
