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.

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 (AT1) 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/m3 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 (10-6 mol/l), an AT1 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 (AT2) 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 - AT1 signaling mediate alterations obesogenic responses in 3T3-L1 adipocytes following exposure to traffic-generated pollution, in combination with a HF diet.