Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice, and the recruitable BAT (rBAT) that resides within white adipose tissue (WAT)6 and skeletal muscle7, that has alternatively been called beige8, brite9, or inducible BAT10. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT10-12. We here provide evidence for a systemically active regulatory mechanism that serves to control whole body BAT-activity for thermoregulation and energy homeostasis. Genetic ablation of type 1A BMP-receptor (Bmpr1A) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between the constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Domain-Based and Overall Life Satisfaction for Youth with Chronic Conditions: The Role of Personal, Interpersonal, and Environmental Factors Over a One-Year Period

This paper examined the differential influences of personal, interpersonal, and environmental level factors on domain-based and overall life satisfaction over one year for youth with chronic health conditions. Baseline and Time 2 follow-up data were used from a study examining quality of life for a sample of 439 youth with chronic conditions, aged 11 to 17 years. The Brief Multidimensional Students’ Life Satisfaction Scale measured youths’ life satisfaction in five domains (i.e., satisfaction with self, family life, friendships, school experiences, where one lives) and in overall life. Six multivariate linear regression analyses were performed, each exploring relations of the hypothesized correlates at baseline with one aspect of life satisfaction at follow-up controlling for youth gender, age, household income, and the corresponding aspect of life satisfaction at baseline. Factors at all three levels were found to be important to some aspect of life satisfaction. Emotional well-being played a notable role in life satisfaction across multiple domains and in overall life satisfaction. Family-related factors were also significantly related to life satisfaction across several domains. Social support from close friends and teachers and the school environment were important to specific domains of life satisfaction. Classmate social support emerged as a key factor related to overall life satisfaction. Implications for practice and future research are discussed

sj-doc-1-jia-10.1177_23259582231210801 - Supplemental material for Short-Form HIV Disability Questionnaire Sensibility, Utility, and Implementation Considerations in Community-Based Settings: A Mixed Methods Study

Supplemental material, sj-doc-1-jia-10.1177_23259582231210801 for Short-Form HIV Disability Questionnaire Sensibility, Utility, and Implementation Considerations in Community-Based Settings: A Mixed Methods Study by Kelly K. O’Brien, Francisco Ibáñez-Carrasco, Patricia Solomon, Soo Chan Carusone, Ann Stewart, Ahmed M. Bayoumi, Darren A. Brown, Adria Quigley, Puja Ahluwalia, Kristine M. Erlandson, Jaime H. Vera, Colm Bergin, Steven E. Hanna, Marilyn Swinton, Brittany Torres, Kiera McDuff, George Da Silva, Glen Bradford, Shaz Islam, Colleen Price, Joanne D. Lindsay, Carolann Murray, Natalia McClellan, Katrina Krizmancic, Praney Anand, Tammy Yates, Rosalind Baltzer Turje, Patrick McDougall, Vladislava Vlatka Maksimcev and Richard Harding in Journal of the International Association of Providers of AIDS Care (JIAPAC)</p

sj-docx-3-jia-10.1177_23259582231210801 - Supplemental material for Short-Form HIV Disability Questionnaire Sensibility, Utility, and Implementation Considerations in Community-Based Settings: A Mixed Methods Study

Supplemental material, sj-docx-3-jia-10.1177_23259582231210801 for Short-Form HIV Disability Questionnaire Sensibility, Utility, and Implementation Considerations in Community-Based Settings: A Mixed Methods Study by Kelly K. O’Brien, Francisco Ibáñez-Carrasco, Patricia Solomon, Soo Chan Carusone, Ann Stewart, Ahmed M. Bayoumi, Darren A. Brown, Adria Quigley, Puja Ahluwalia, Kristine M. Erlandson, Jaime H. Vera, Colm Bergin, Steven E. Hanna, Marilyn Swinton, Brittany Torres, Kiera McDuff, George Da Silva, Glen Bradford, Shaz Islam, Colleen Price, Joanne D. Lindsay, Carolann Murray, Natalia McClellan, Katrina Krizmancic, Praney Anand, Tammy Yates, Rosalind Baltzer Turje, Patrick McDougall, Vladislava Vlatka Maksimcev and Richard Harding in Journal of the International Association of Providers of AIDS Care (JIAPAC)</p