Mechanisms of obesogenic adipocyte signaling in mouse 3T3-L1 cells in response to plasma from C57BL/6 mice exposed to traffic-generated emissions and high-fat diet.
This study suggests that exposure to traffic pollution and a high-fat diet may promote obesity through Ang II signaling in adipocytes, but further research is needed to confirm these effects in humans.
Where it sits
this study against the rest of the snap-8 corpusSummary and findings
This study investigated the effects of plasma from C57BL/6 mice exposed to traffic-generated emissions and high-fat diets on adipocyte signaling in 3T3-L1 cells. The research focused on the role of angiotensin II (Ang II) and its receptors in mediating obesogenic outcomes. Not reported in abstract.
Abstract
Recent studies have demonstrated a strong correlation between exposure to traffic-generated air pollutants and the development of metabolic disorders, including obesity. We have reported that exposure to a mixture of vehicle emissions (MVE) promotes increased angiotensin II (Ang II) levels, associated with adipocyte hypertrophy and lipid accumulation in C57BL/6 mice; and this effect is further exacerbated by high-fat (HF) diet consumption. To elucidate the underlying mechanisms, mouse adipocyte 3T3-L1 cells were utilized to test the hypothesis that circulating Ang II mediates obesogenic outcomes via the Ang II type 1 (AT<sub>1</sub>) receptor following MVE exposure. Plasma from three mo-old male C57BL/6 mice, fed either a high-fat (HF) or low-fat (LF) diet and exposed to either filtered-air (FA) or 100 µg PM/m<sup>3</sup> MVE for 6 hr/day for 30 days was collected and applied to the cell culture media (1:40 dilution) for 48 hrs. A subset of cells was pretreated with losartan (10<sup>-6</sup> mol/l), an AT<sub>1</sub> receptor antagonist, for 30 min. 3T3-L1 adipocytes treated with plasma from either HF diet-fed or MVE-exposed animals, regardless of diet, exhibited adipocyte hypertrophy. Plasma from the MVE + HF diet group induced increased adipocyte mRNA expression of the Ang II type 2 (AT<sub>2</sub>) receptor, angiotensinogen (AGT), glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor gamma (PPARγ) and leptin, compared to either the LF or HF + FA controls; most of these effects were normalized by losartan treatment. These findings indicate that Ang II - AT<sub>1</sub> signaling mediate alterations obesogenic responses in 3T3-L1 adipocytes following exposure to traffic-generated pollution, in combination with a HF diet.
Background
This paper addresses the relationship between traffic-generated air pollutants and metabolic disorders, particularly obesity. Prior studies have linked air pollution exposure to increased metabolic syndrome risk, but the specific mechanisms remain unclear. Understanding how these pollutants affect adipocyte function is crucial for developing preventive strategies against obesity.
Methods
The study utilized mouse adipocyte 3T3-L1 cells and plasma from three-month-old male C57BL/6 mice. The mice were fed either a high-fat or low-fat diet and exposed to filtered air or 100 µg PM/m^3 MVE for 6 hours daily over 30 days. The primary outcome measured was adipocyte hypertrophy and gene expression changes after 48 hours of plasma exposure.
Results
3T3-L1 adipocytes treated with plasma from the MVE + HF diet group exhibited increased adipocyte mRNA expression of several genes associated with obesity. Losartan treatment normalized most of these effects. Specific numeric findings were not reported in the abstract.
Interpretation
The findings suggest that Ang II - AT<sub>1</sub> signaling plays a role in mediating obesogenic responses in adipocytes following exposure to traffic pollution. While the study indicates significant alterations in gene expression, the clinical relevance remains uncertain due to the lack of human data and reliance on rodent models. The small sample size and in vitro nature of the study limit the ability to generalize the results to human populations.
Key findings
- Increased adipocyte mRNA expression of Ang II type 2 receptor, angiotensinogen, GLUT-4, PPARγ, and leptin compared to LF or HF+FA controls.
- Most effects were normalized by losartan treatment (10^-6 mol/l).
- Mice were exposed to 100 µg PM/m^3 MVE for 6 hr/day for 30 days.
Limitations
- Rodent-only evidence, no human data.
- In vitro study, limiting direct clinical applicability.
- Short exposure duration of 30 days may not reflect long-term effects.
- Small sample size of plasma sources not detailed.