Related Experiment Video
Updated: Feb 6, 2026
A Simple and Efficient Method to Detect Nuclear Factor Activation in Human Neutrophils by Flow Cytometry
Published on: April 9, 2013
Nuclear factor erythroid 2-related factor 2 activation mediates hyperhomocysteinemia-associated lipolysis suppression
Xin Li1, Yuhong Cheng2, Xiuli Zhong1
11 College of Medical Laboratory Science and Technology, Harbin Medical University (Daqing), Daqing 163319, Heilongjiang, P. R. China.
Abstract:
Hyperhomocysteinemia (HHcy) is associated with suppressed lipolytic response in adipocytes/adipose tissue, however, the underlying mechanism remains to be extensively studied. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcriptional factor regulating antioxidant generation, has been recently reported to mediate lipid metabolism. Employing both fully differentiated 3T3-L1 adipocytes and male C57BL/6 mice, in the present study, we investigated the potential involvement of Nrf2 activation in HHcy-mediated lipolytic suppression. Our results showed that homocysteine (Hcy) treatment resulted in suppressed lipolysis, evidenced by increased intracellular triglyceride (TG) accumulation, decreased glycerol and free fatty acid (FFA) in fully differentiated 3T3-L1 adipocytes. Interestingly, Hcy exposure was associated with Nrf2 activation in adipocytes. Further studies showed that Nrf2 knockdown via siRNA transfection ameliorated Hcy-induced glycerol release in adipocytes. On the contrary, Nrf2 activators, epigallocatechin gallate (EGCG) and tert-butylhydroquinone (t-BHQ), increased intracellular TG content and decreased glycerol release in adipocytes. Importantly, our in vitro observations were corroborated by our in vivo findings, in which Hcy feeding (0.1% wt/vol) for four weeks induced Nrf2 expression in adipose tissue and lowered circulating FFA and glycerol levels in mice. Furthermore, EGCG injection (5 mg/kg/d) decreased circulating glycerol levels in comparison to the control group in mice. In conclusion, these results indicated that Nrf2 activation in response to HHcy plays an important role in mediating Hcy-suppressed lipolysis in adipocytes.
Insights
Hyperhomocysteinemia (HHcy) suppresses fat breakdown (lipolysis) by activating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in fat cells. This study reveals Nrf2
Area of Science:
- Metabolism
- Cell Biology
- Molecular Biology
Background:
- Hyperhomocysteinemia (HHcy) is linked to reduced lipolysis in adipose tissue, but the mechanisms are unclear.
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant responses and lipid metabolism.
Purpose of the Study:
- To investigate the role of Nrf2 activation in HHcy-induced suppression of lipolysis.
- To explore the therapeutic potential of targeting Nrf2 in HHcy-related metabolic dysfunction.
Main Methods:
- Utilized 3T3-L1 adipocytes and C57BL/6 mice models.
- Assessed lipolysis markers (triglyceride, glycerol, free fatty acids) under homocysteine (Hcy) treatment.
- Investigated Nrf2 expression and activity using siRNA knockdown and Nrf2 activators (EGCG, t-BHQ).
Main Results:
- Hcy treatment suppressed lipolysis in adipocytes, increasing triglyceride accumulation and decreasing glycerol/FFA release.
- Hcy exposure activated Nrf2 in adipocytes, and Nrf2 knockdown ameliorated Hcy-induced lipolysis suppression.
- Nrf2 activators (EGCG, t-BHQ) mimicked Hcy effects by increasing TG and decreasing glycerol release.
- In vivo studies confirmed Hcy-induced Nrf2 expression in adipose tissue and reduced circulating FFA/glycerol in mice.
Conclusions:
- Nrf2 activation plays a significant role in mediating HHcy-induced suppression of lipolysis in adipocytes.
- Targeting Nrf2 may offer a novel therapeutic strategy for managing metabolic disturbances associated with HHcy.
Related Concept Videos
02:16Transcription Factors
01:17Factors Affecting Activity Coefficient
The activity coefficient value for an ion is close to one when the solution has almost zero ionic strength, i.e., when the solution shows close to ideal behavior. As the ionic strength of the solution increases from 0 to 0.1 mol/L, a...
04:01Factors Affecting Solubility
03:08Electrolytes: van't Hoff Factor
The colligative properties of a solution depend only on the number, not on the identity, of solute species dissolved. The concentration terms in the equations for various colligative properties (freezing point depression, boiling point elevation, osmotic pressure) pertain to all solute species present in the solution. Nonelectrolytes dissolve physically without dissociation or any other accompanying process. Each molecule that dissolves yields one...
02:35Transcription Elongation Factors
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
01:13meta-Directing Deactivators: –NO2, –CN, –CHO, –CO2R, –COR, –CO2H