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postgraduate thesis: Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity
Title | Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity |
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Authors | |
Advisors | |
Issue Date | 2013 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Lee, P. [李佩芝]. (2013). Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5194748 |
Abstract | Background and objectives:
A lot of studies proved that adipocyte fatty acid binding protein (A-FABP), an adipokine mainly expressed in adipocytes and macrophages, is the key link between obesity and inflammation which is suggested to be a therapeutic target for obesity-related diseases. Loss-of-function study was employed by using A-FABP knockout (KO) mice generated by our group to investigate role of A-FABP in high fat high cholesterol (HFHC) diet-induced obesity.
Key findings:
1. Our study confirmed that HFHC diet-induced A-FABP KO mice have a significantly increased body weight when compared to the wild-type (WT) control mice.
2. Higher adiposity was the major reason for the A-FABP KO mice to be heavier than the WT controls under HFHC diet induction.
3. The marked increase of the weight of subcutaneous fat and peri-renal fat contributed to the higher adiposity of the HFHC-diet induced A-FABP KO mice when compared to the WT controls.
4. The HFHC-diet induced A-FABP KO mice significantly consumed less oxygen and produced less carbon dioxide suggesting the reduced energy expenditure but had higher weekly energy intake when compared with the WT controls, leading to higher adiposity.
5. The A-FABP KO mice were protected against HFHC diet induced glucose intolerance, insulin resistance, hyperglycemia and hyperinsulinemia when compared with the WT controls. There was also a better insulin secretion in response to glucose stimulation in A-FABP KO mice under prolonged HFHC diet induction when compared with the WT controls.
6. The A-FABP KO mice were protected against the development of hypercholesterolemia and hypertriglycemia when compared the WT controls under HFHC diet induction. However, there was no significant difference in the fasting serum free fatty acids (FFA) level among A-FABP WT and KO mice fed with standard chow (STC) or HFHC diet.
7. A-FABP KO mice were protected against isolated systolic hypertension (ISH) under HFHC diet induction.
8. The A-FABP KO mice were protected against HFHC diet-induced liver injury as indicated by a lower serum ALT level suggesting a better liver function when compared with the WT controls.
9. Under HFHC diet induction, M1 macrophage polarization was dominant in fat tissues of A-FABP WT mice but M2 macrophage polarization was dominant in fat tissues of A-FABP KO mice, suggesting an improved inflammatory status in the adipose tissue of the A-FABP KO mice when compared with the WT controls. This may also be the reason for why HFHC diet-induced A-FABP KO mice have an increased body weight but are metabolically healthier compared to their WT controls.
Conclusions:
A-FABP KO mice had a significant higher body weight and higher adiposity due to the reduced energy expenditure and increased weekly food intake as indicated in the metabolic cage study and the reason for metabolic healthier is due to the alleviated HFHC diet induced M1 macrophage polarization in various adipose tissues suggesting an improved inflammatory status in A-FABP KO mice comparing to the WT controls. |
Degree | Master of Philosophy |
Subject | Cytokines Fat cells Adipose tissues Obesity - Animal models |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/197517 |
HKU Library Item ID | b5194748 |
DC Field | Value | Language |
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dc.contributor.advisor | Xu, A | - |
dc.contributor.advisor | Hoo, RLC | - |
dc.contributor.author | Lee, Pui-chi | - |
dc.contributor.author | 李佩芝 | - |
dc.date.accessioned | 2014-05-27T23:16:40Z | - |
dc.date.available | 2014-05-27T23:16:40Z | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Lee, P. [李佩芝]. (2013). Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5194748 | - |
dc.identifier.uri | http://hdl.handle.net/10722/197517 | - |
dc.description.abstract | Background and objectives: A lot of studies proved that adipocyte fatty acid binding protein (A-FABP), an adipokine mainly expressed in adipocytes and macrophages, is the key link between obesity and inflammation which is suggested to be a therapeutic target for obesity-related diseases. Loss-of-function study was employed by using A-FABP knockout (KO) mice generated by our group to investigate role of A-FABP in high fat high cholesterol (HFHC) diet-induced obesity. Key findings: 1. Our study confirmed that HFHC diet-induced A-FABP KO mice have a significantly increased body weight when compared to the wild-type (WT) control mice. 2. Higher adiposity was the major reason for the A-FABP KO mice to be heavier than the WT controls under HFHC diet induction. 3. The marked increase of the weight of subcutaneous fat and peri-renal fat contributed to the higher adiposity of the HFHC-diet induced A-FABP KO mice when compared to the WT controls. 4. The HFHC-diet induced A-FABP KO mice significantly consumed less oxygen and produced less carbon dioxide suggesting the reduced energy expenditure but had higher weekly energy intake when compared with the WT controls, leading to higher adiposity. 5. The A-FABP KO mice were protected against HFHC diet induced glucose intolerance, insulin resistance, hyperglycemia and hyperinsulinemia when compared with the WT controls. There was also a better insulin secretion in response to glucose stimulation in A-FABP KO mice under prolonged HFHC diet induction when compared with the WT controls. 6. The A-FABP KO mice were protected against the development of hypercholesterolemia and hypertriglycemia when compared the WT controls under HFHC diet induction. However, there was no significant difference in the fasting serum free fatty acids (FFA) level among A-FABP WT and KO mice fed with standard chow (STC) or HFHC diet. 7. A-FABP KO mice were protected against isolated systolic hypertension (ISH) under HFHC diet induction. 8. The A-FABP KO mice were protected against HFHC diet-induced liver injury as indicated by a lower serum ALT level suggesting a better liver function when compared with the WT controls. 9. Under HFHC diet induction, M1 macrophage polarization was dominant in fat tissues of A-FABP WT mice but M2 macrophage polarization was dominant in fat tissues of A-FABP KO mice, suggesting an improved inflammatory status in the adipose tissue of the A-FABP KO mice when compared with the WT controls. This may also be the reason for why HFHC diet-induced A-FABP KO mice have an increased body weight but are metabolically healthier compared to their WT controls. Conclusions: A-FABP KO mice had a significant higher body weight and higher adiposity due to the reduced energy expenditure and increased weekly food intake as indicated in the metabolic cage study and the reason for metabolic healthier is due to the alleviated HFHC diet induced M1 macrophage polarization in various adipose tissues suggesting an improved inflammatory status in A-FABP KO mice comparing to the WT controls. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.subject.lcsh | Cytokines | - |
dc.subject.lcsh | Fat cells | - |
dc.subject.lcsh | Adipose tissues | - |
dc.subject.lcsh | Obesity - Animal models | - |
dc.title | Phenotypic characterization of adipocyte fatty acid binding protein knockout mice under high fat high cholesterol diet-induced obesity | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b5194748 | - |
dc.description.thesisname | Master of Philosophy | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_b5194748 | - |
dc.identifier.mmsid | 991036877579703414 | - |