Acute Modulation of Adipose Tissue Lipolysis by Intravenous Estrogens

Objective: The aim of this study was to determine whether intravenous (IV) conjugated estrogens (EST) acutely enhance the suppression of whole-body or regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal women. Research Methods and Procedures: We assessed whole-body lipolysis by [2H5]glycerol rate of appearance (GlycRA) and abdominal and femoral SAT lipolysis (interstitial glycerol; GlycIS) by subcutaneous microdialysis. Postmenopausal women (n = 12) were studied on two occasions, with IV EST or saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40 mU/m2/ min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and recovery of [13C] glycerol during microdialysis were used to assess blood flow changes and interstitial glycerol concentrations, respectively. Results: Compared with CON, EST did not affect systemic basal or insulin-mediated suppression of lipolysis (GlycRA) or SAT nutritive blood flow. Basal GlycIS in SAT was reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT was not significantly influenced by EST. Discussion: These findings suggest that estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but do not alter whole-body or SAT suppression of lipolysis by insulin. Originally published Obesity (Silver Spring), Vol. 14, No. 12, Dec 200

Increasing Dietary Fat Elicits Similar Changes in Fat Oxidation and Markers of Muscle Oxidative Capacity in Lean and Obese Humans

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m2, age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m2, 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity

Perspectives of LGBTQ Older Adults on Aging in Place: A Qualitative Investigation

This qualitative study conducted by a community-research partnership used multiple types of data collection to examine variables relevant for LGBTQ older adults who wished to age in place in their urban Denver neighborhood. Focus groups, interviews, and a town hall meeting were used to identify barriers and supports to aging in place. Participants (N = 73) identified primarily as lesbian or gay, aged 50–69, and lived with a partner. Ageism, heterosexism, and cisgenderism emerged as cross-cutting themes that negatively impact access to health care, housing, social support, home assistance, and legal services. Resilience from weathering a lifetime of discrimination was identified as a strength to handle aging challenges. Recommendations for establishing an aging in place model included establishing welcoming communities and resource centers and increasing cultural competence of service providers. This study provides a unique contribution to understanding the psychosocial, medical, and legal barriers for successfully aging in place

Bisphosphonate Drug Holiday and Fracture Risk

Background/Aims: Among women with ≥ 3 years exposure to bisphosphonates (BPs), we compared the incidence of fragility fractures in those who discontinued BPs for ≥ 12 months (drug holiday) to those who continued to use BPs (persistent use). Methods: This retrospective cohort study included women aged ≥ 45 years who initiated BP use from four Kaiser Permanente regions between January 1, 1998, and December 31, 2009. Drug holiday was defined as ≥ 12 months with BP use at 0% adherence. Persistent use status required ongoing use at ≥ 50% adherence. The primary outcome of interest was the first occurrence of an incident clinical osteoporosis-related fragility fracture, identified from the electronic medical record (EMR) via ICD-9-CM codes. All subjects were followed until fracture, disenrollment from the health plan, death, or December 31, 2012. From the EMR, we collected information on the following potential confounders and effect modifiers: race/ethnicity, age, body mass index, comorbidities, history of previous fragility fracture, lowest T-score prior to cohort entry, fall risk, 10-year fracture risk, and prior/concomitant use of bone-active medications. Persistent users and drug holiday subjects were compared with regard to several demographic and clinical characteristics. Time-varying Cox proportional hazards models were used to compare osteoporosis-related fracture incidence between the two groups. Results: The cohort of 28,620 women, observed for 111,997 person-years, included 17,123 (59.8%) persistent BP users and 11,497 (40.2%) drug holiday subjects. The drug holiday group had fewer comorbidities, higher baseline T-scores, and lower fracture and fall risk scores. A total of 3,571 osteoporosis-related fractures were observed. The unadjusted rate ratio (RR) for any osteoporosis-related fractures for drug holiday compared to persistent use was 0.87 (95% confidence interval [CI]: 0.81–0.94), but was 1.0 (95% CI: 0.9–1.2) for hip fractures only. The time-varying models suggested no differences in fracture risk (hazard ratio [HR]: 0.90, 95% CI: 0.80–1.00) after adjustment for baseline fall and fracture risk, comorbidities and other bone-active medication use. Similarly, no difference in hip fracture risk was observed (HR: 0.84, 95% CI: 0.68–1.03). Discussion: Women who undertake a holiday from BP use are not at greater risk of osteoporosis-related fragility fractures, nor hip fractures specifically, than are women who continue to use BPs persistently

Plasma FFA (± SE; Left) and triglycerides (± SE; Right) during LF (Top) and HF (Middle) diets in LN (N = 10; dashed line), and OB (N = 9; solid line).

<p>24 h FFA and triglycerides areas under the curve (AUC) are presented in the bottom graphs.</p

Mean (± SE) Protein (Top), carbohydrate (Middle), and fat (Bottom) oxidation (g/kg FFM/day) measured using room calorimetry during LF (black bars) and HF (grey bars) in LN (N = 10) and OB (N = 9).

<p>* LF significantly different from HF (P<0.05).</p

Mean (± SE) total (Top) and phosphorylated (Bottom) AMPK protein during LF (black bars) and HF (grey bars) in LN (N = 5) and OB (N = 6).

<p>Representative blots are show above the graphs. * LF significantly different from HF (P<0.05).</p

mRNA results (au, mean±SE).

1<p>OB > LN.</p>2<p>LF > HF.</p>3<p>LF < HF.</p