The Effect of a Reduced-Calorie Diet on alpha-2 Adrenergic Receptor Responsiveness in Abdominal Adipose Tissue in Obese Men During Exercise

There is at present an imperfect understanding of the effect of diet on availability of inhibitory receptors in fat cells during exercise among obese men. 

*Objective:* The purpose of this study was to determine whether diet results in downregulation of alpha-2 adrenergic receptor ([alpha]~2-AR~) messenger RNA (mRNA), improving metabolism in exercise in obese men. 

*Design:* One group, pre-test, post-test design.

*Measurements:* Subcutaneous abdominal adipose tissue was tested for physiologic response, such as changes in catecholamines and other markers of lipolysis measured during periods of exercise, before and after a 12-week diet. Plasma markers of lipolysis/antilipolytic activity (catecholamines [adrenaline and noradrenaline], NEFA, lactate, glucose, hematocrit, or insulin levels) were analyzed at four points in time in order to determine the effect of exercise on [alpha]~2-AR~ and [beta]-AR responsiveness to sympathetic stimulation.

*Subjects:* Otherwise healthy 18 to 45 year old obese men (defined as a body mass index (BMI) over 33 kg/m^2^).

*Results:* The 12-week reduced calorie diet did not result in improved metabolism. Instead, upregulation of alpha-2 adrenergic receptor ([alpha]~2-AR~) messenger RNA (mRNA) was observed. On average, [alpha]~2-AR~ mRNA levels (ratio of [alpha]~2-AR~ to cyclophilin) in subjects increased by 0.022-0.023 after the diet. The average differences in of [alpha]~2-AR~ mRNA and [beta]-AR mRNA measured before and after diet were both insignificant (M = 0.015) t(4) = -0.911; _P_ > 0.05; (M = 0.0139; t(4) = 0.077; _P_ > 0.05). 

*Conclusion:* The observed direction of change in [alpha]~2-AR~ mRNA levels, when viewed together with the stability of [beta]-AR mRNA levels, suggests that upregulation of [alpha]~2-AR~ rather than downregulation occurred. Downregulation would account for decreased lipolytic activity during exercise, future study is needed

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence