Citations

Background: Although a gradual increase in heart rate (HR) during dobutamine stress testing (DST) is desired, few data exists regarding whether this is similarly achieved in patients of widely varying body mass index (BMI). Whether difference in BMI contributes to variation in the hemodynamic and symptomatic response to dobutamine is also unknown. Methods: From prospectively acquired data of 2776 consecutive patients who underwent DST according to standard weight-based clinical protocol, we classified patients into 4 groups of BMI (kg/m 2 ): <25 (normal), 25 to 29.9 (overweight), 30 to 39.9 (obese), and ≥40 (severely obese) and compared the rate of increase of HR, mean blood pressure, and development of symptoms for the groups. Results: Age was 68 + 12 years, 52% were men, BMI was 29.8 + 6.6 kg/m 2 (range 14.5-81.4), 198 (7%) had BMI ≥40, and target HR was achieved in 2433 (88%). The rate of increase in HR was similar for each group of BMI after adjustment for age, gender, baseline HR, negative chronotropic use, and atropine administration. The percentage of patients in each group who achieved target HR was similar and the percentage of target HR achieved at each stage of dobutamine was essentially equivalent. Blood pressure responses and development of symptoms were similar in the 4 groups of BMI. Independent predictors of failure to achieve target HR included age, diabetes mellitus, treatment with negative chronotropic medications, and baseline HR; BMI was not a predictor (odds ratio [OR] 0.98, P = .086). Conclusion: The current weight-based protocol of dobutamine dosing for DST results in similar increases in HR and blood pressure for patients of widely varying BMI.

A session about educating translational scientists was held at a 2010 NIH forum on promoting collaborations between academia, government, and industry.

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1 + /CD45 − /Mac1 − ; referred to as Sca-1 + progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1 + cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.