Black/White Disparities in Obesity Widen with Increasing Rurality: Evidence from a National Survey.

Background: Racial health disparities in obesity and obesity-related conditions and behaviors are well documented, although a small body of research suggests that geographic factors (e.g., socioeconomic status [SES] and rural/urban status) may alter the magnitude of these disparities. Methods: This study explored how rurality moderates black/white health disparities using a nationally representative sample from the 2012 Behavioral Risk Factor Surveillance System (n=359,157). Respondents' county of residence was linked to the U.S. Census information to obtain the county-level Index of Relative Rurality (IRR). Weighted logistic regression was used to model obesity, diabetes, and lack of physical activity (PA) on race (black/white), IRR, and an interaction term of race and IRR, including covariates (age, sex, education, marital status, employment, and income). Results: Blacks were significantly more likely to have obesity, diabetes, and a lack of PA compared with whites. Irrespective of race, rural respondents were significantly more likely to have obesity (odds ratio [OR] 1.035, confidence interval [95% CI] 1.028-1.043) and a lack of PA (OR 1.045, 95% CI 1.038-1.053) than respondents in more urban areas. For obesity and diabetes, the interaction term for black×IRR quintile was significant and positive, indicating an increase in the magnitude of the black/white disparity with increasing rurality. Discussion: These findings underscore the need for policies and programs aimed to reduce racial disparities in obesity and related conditions to consider the geographic context in which these outcomes occur.

Redox regulation of Rac1 by thiol oxidation.

The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys(18)) that can be selectively oxidized at physiological pH because of its lowered pKa. Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys(18) by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1(C18D). We also evaluated Rac1(C18S) as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1(WT) but is resistant to thiol oxidation. In addition, Rac1(C18D), but not Rac1(C18S), shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1(C18D) in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1(C18D) in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1(WT) and the redox-insensitive Rac1(C18S) variant. Moreover, expression of Rac1(C18D) in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys(18) is a novel posttranslational modification that upregulates Rac1 activity.