Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults.

OBJECTIVE: To determine whether aerobic exercise training + weight loss (AEX + WL) would affect the expression of myostatin and its relationship with insulin sensitivity in a longitudinal, clinical intervention study. DESIGN AND METHODS: Thirty-three obese sedentary postmenopausal women and men (n = 17 and 16, age: 61 ± 1 years, body mass index: 31 ± 1 kg/m(2) , VO2 max: 21.9 ± 1.0 mL/kg/min, X ± Standard error of the mean (SEM)) completed 6 months of 3 days/week AEX + WL. During an 80 mU m(-2) min(-1) hyperinsulinemic-euglycemic clamp, we measured glucose utilization (M), myostatin, myogenin, and MyoD gene expression by real-time RT-PCR in vastus lateralis muscle at baseline and 2 h. RESULTS: Body weight (-8%) and fat mass (-17%) decreased after AEX + WL (P < 0.001). Fat-free mass (FFM) and mid-thigh muscle area by computed tomography did not change but muscle attenuation increased (P < 0.05). VO2 max increased 14% (P < 0.001). AEX + WL increased M by 18% (P < 0.01). Myostatin gene expression decreased 19% after AEX + WL (P < 0.05). Basal mRNA myostatin levels were negatively associated with M before the intervention (r = -0.43, P < 0.05). Insulin infusion increased myoD and myogenin expression before and after AEX + WL (both P < 0.001) but basal levels did not change. The insulin effect on myostatin expression was associated with the change in M after AEX + WL (r = 0.56, P < 0.005). CONCLUSIONS: Exercise and weight loss results in a downregulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women.

IMPACT OF WEIGHT LOSS AND AEROBIC EXERCISE ON NUTRITION AND BONE MINERAL DENSITY IN AFRICAN AMERICAN AND CAUCASIAN POSTMENOPAUSAL WOMEN.

BACKGROUND: Weight loss is often recommended for obese women to reduce fat mass and the risk of developing chronic diseases, but may result in a reduction of bone mineral density (BMD). African Americans have greater BMD than Caucasians, but differences in the decrease in BMD between these races following weight reduction with and without exercise are unknown. OBJECTIVES: The purpose of this study was to investigate the hypothesis that Caucasian women would lose greater amounts of BMD than African American women after undergoing weight loss, but that the addition of aerobic exercise would attenuate the loss in both races. DESIGN: Longitudinal. PARTICIPANTS: African American (n=34) and Caucasian (n=63), overweight and obese postmenopausal (age 45-80 years). INTERVENTION: Six months of weight loss (250-350 kcal/days deficit) alone (WL) or in combination with aerobic exercise consisting of 3 days/week treadmill training at >85% of heart rate reserve for 45 min (AEX+WL). MEASUREMENTS: Femoral neck, total femur, and lumbar BMD, VO2max, urinary calcium, and dietary intake. RESULTS: African American women had a greater body weight, BMI, and BMD all sites and lower dietary protein and calcium intakes than Caucasian women (all P<0.05). Weight decreased 7.5% in both groups and VO2max increased only after AEX+WL (intervention effect, P<0.001). Both races lost ~1% of their femoral neck and total femur BMD following the interventions (P's<0.01). There were no race by intervention interactions. There was a trend for the women undergoing WL to lose greater femoral neck BMD than those in AEX+WL (P=0.07). There were no associations between changes in BMD and changes in VO2max, urinary calcium, or dietary intake. CONCLUSIONS: Our data indicate that despite beginning the interventions with greater BMD than Caucasian postmenopausal women, African Americans were not spared from losses of femoral neck and total femur BMD following six months of weight loss, but that addition of aerobic exercise to weight loss tends to attenuate the decreases in femoral neck BMD in both races.

Novel neuropeptide Y1 and Y5 receptor gene variants: associations with serum triglyceride and high-density lipoprotein cholesterol levels.

Neuropeptide Y (NPY) appears to play a critical role in the integration of appetite and energy expenditure through NPY Y1 and Y5 receptor subtypes. Moreover, the NPY Y1 receptor is highly expressed on human adipocytes, where it inhibits lipolysis. The genes encoding these receptors are transcribed co-ordinately in opposite directions from a common promoter in a region of chromosome 4 that has been previously linked to triglyceride and small low-density lipoprotein (LDL) particle concentration. Therefore, the purpose of this investigation was to examine the relationship between polymorphisms in the genes encoding NPY Y1 and Y5 and the development of obesity and dyslipidemia. We screened the promoter and coding regions and identified four polymorphic variants. One of these, a cytosine to thymine (C-->T) substitution in the untranslated region between the genes for NPY Y1 and Y5 (allele frequency 0.11), was significantly associated with both lower fasting triglyceride level (152 vs 125 mg/dl), and higher high-density lipoprotein (HDL) concentrations (49 vs 45 mg/dl) (p < 0.01) in 306 obese subjects. Given the stimulatory effect of NPY on adipocyte lipoprotein lipase (LPL) activity, and the lack of association of other polymorphisms with serum lipid levels, we hypothesize that this is a gain-in-function polymorphism.

Bisoprolol, a once-a-day beta-blocking agent for patients with mild to moderate hypertension.

The 24-h blood pressure control of bisoprolol, a new beta-selective, beta-blocking agent, was studied in 240 mild to moderate hypertensive patients in this 4-week, randomized, double-blind, placebo-controlled trial. A once-daily dosing schedule was evaluated by comparing bisoprolol's antihypertensive effectivness and safety at 24 h postdose and 3 h postdose, the latter time intended to correspond to peak effectiveness. Results from this trial demonstrated the antihypertensive effectiveness of once-daily bisprolol at doses ranging from 5-20 mg. Mean reductions from baseline diastolic blood pressure, measured 24 h postdose, were 6.3, 8.8, and 10.1 mmHg for patients receiving bisoprolol 5, 10, and 20 mg, respectively, compared with 1.6 mmHg for placebo-treated patients (p < 0.01); mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6, 8.6, and 10.9 mmHg, respectively, versus 3.3 mmHg for placebo (p < or = 0.01); and mean reductions from baseline heart rate for the bisoprolol groups were 5.1, 7.1, and 10.2 beats/min, respectively, compared with a 0.9 beats/min increase in heart rate for the placebo group (p < 0.01). The response rates for bisoprolol-treated patients ranged from 47 to 70% compared with 18% for patients on placebo (p < 0.01). Antihypertensive effects were dose-related and sustained over the 24-h dosing interval. Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial.(ABSTRACT TRUNCATED AT 250 WORDS)