Norepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [C] MRB.

The energy-dissipating properties of brown adipose tissue (BAT) have been proposed as therapeutic targets for obesity and diabetes. Little is known about basal BAT activity. Capitalizing on the dense sympathetic innervation of BAT, we have previously shown that BAT can be detected in humans under resting room temperature (RT) conditions by using (S,S)-C-O-methylreboxetine (MRB), a selective ligand for the norepinephrine transporter (NET).

Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

Context: Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses.

Objective: To examine the potential role of brain noradrenergic (NA) activation in humans during hypoglycemia.

Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis and tuberculin skin test conversion among prisoners.

Poor vitamin D status has been associated with tuberculosis (TB); whether poor status is cause or consequence of disease is uncertain. We conducted a case-control study and two nested case-control studies to determine whether vitamin D levels were associated with active TB, tuberculin skin test (TST) conversion, and risk of progression to the active TB in prisoners in Brazil. In multivariable conditional logistic regression, subnormal vitamin D levels (OR, 3.

The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons.

Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels.

Imaging human brown adipose tissue under room temperature conditions with (11)C-MRB, a selective norepinephrine transporter PET ligand.

Introduction: Brown adipose tissue (BAT) plays a critical role in adaptive thermogenesis and is tightly regulated by the sympathetic nervous system (SNS). However, current BAT imaging modalities require cold stimulation and are often unreliable to detect BAT in the basal state, at room temperature (RT). We have shown previously that BAT can be detected in rodents under both RT and cold conditions with (11)C-MRB ((S,S)-(11)C-O-methylreboxetine), a highly selective ligand for the norepinephrine transporter (NET).

A pilot study: the importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome.

Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism.

Glucose utilization rates regulate intake levels of artificial sweeteners.

It is well established that animals including humans attribute greater reinforcing value to glucose-containing sugars compared to their non-caloric counterparts, generally termed 'artificial sweeteners'. However, much remains to be determined regarding the physiological signals and brain systems mediating the attribution of greater reinforcing value to sweet solutions that contain glucose. Here we show that disruption of glucose utilization in mice produces an enduring inhibitory effect on artificial sweetener intake, an effect that did not depend on sweetness perception or aversion.

Blood pressure hyperreactivity: an early cardiovascular risk in normotensive men exposed to low-to-moderate inorganic arsenic in drinking water.

Background: Essential hypertension is associated with chronic exposure to high levels of inorganic arsenic in drinking water. However, early signs of risk for developing hypertension remain unclear in people exposed to chronic low-to-moderate inorganic arsenic.

Objective: We evaluated cardiovascular stress reactivity and recovery in healthy, normotensive, middle-aged men living in an arsenic-endemic region of Romania.

Response to acute psychophysical stress and 24-hour glycemic control in healthy older people.

We examined the relation between stress reactivity and 24 h glycemic control in 17 inactive, healthy older people (≥60 years) under both a novel psychophysical stress and a seated control condition. Plasma cortisol was measured over the course of the stress and recovery periods. Glycemic control was determined over the subsequent 3 h from an oral glucose tolerance test (OGTT) and over 24 h via continuous glucose monitoring (CGM).

Ex vivo and in vivo evaluation of the norepinephrine transporter ligand [11C]MRB for brown adipose tissue imaging.

Introduction: It has been suggested that brown adipose tissue (BAT) in humans may play a role in energy balance and obesity. We conducted ex vivo and in vivo evaluation using [(11)C]MRB, a highly selective NET (norepinephrine transporter) ligand for BAT imaging at room temperature, which is not achievable with [(18)F]FDG.

Methods: PET images of male Sprague-Dawley rats with [(18)F]FDG and [(11)C]MRB were compared.

The gut-brain dopamine axis: a regulatory system for caloric intake.

Post-ingestive factors are known to strongly modulate feeding behavior by providing feedback signals to the central nervous system on the current physiological state of the organism. Of particular interest is the identification of the physiological pathways that permit the brain to sense post-ingestive signals. We will review recent evidence supporting the concept that direct stimulation of the gastrointestinal tract with nutrients induces release of the catecholamine neurotransmitter dopamine.

Regulation of fat intake in the absence of flavour signalling.

Animals, including humans, can achieve precise regulation of caloric intake by adjusting consumption in response to covert changes in energy density. It remains unknown, however, whether the presence of flavour cues are required for the ability to maintain constant caloric intake. Also unknown are the brain circuits that may function as the central calorie monitors that control adaptive adjustments in energy intake.

Effects of ad libitum ingestion of monosodium glutamate on weight gain in C57BL6/J mice.

Although the umami compound monosodium glutamate (MSG) is a widely used flavor enhancer, controversy still persists regarding the effects of MSG intake on body weight. It has been claimed, in particular, that chronic MSG intake may result in excessive body weight gain and obesity. In this study we assessed the effects of chronic (16 weeks) ad libitum MSG on body weight and metabolism of C57BL6/J mice.

Nutrient selection in the absence of taste receptor signaling.

When allowed to choose between different macronutrients, most animals display a strong attraction toward carbohydrates compared with proteins. It remains uncertain, however, whether this food selection pattern depends primarily on the sensory properties intrinsic to each nutrient or, alternatively, metabolic signals can act independently of the hedonic value of sweetness to stimulate elevated sugar intake. Here we show that Trpm5(-/-) mice, which lack the cellular mechanisms required for sweet and several forms of l-amino acid taste transduction, develop a robust preference for d-glucose compared with isocaloric l-serine independently of the perception of sweetness.

Greater exercise sweating in obese women with polycystic ovary syndrome compared with obese controls.

Purpose: We examined estradiol and testosterone effects on thermoregulation in women with and without Polycystic Ovary syndrome (PCOS). We hypothesized that core temperature (Tc) threshold for sweating during exercise is delayed in women with PCOS and that testosterone delays the Tc set point for sweating during exercise.

Methods: For 16 d, we suppressed estrogens, progesterone, and testosterone with a gonadotropin-releasing hormone antagonist (GnRHant) in seven women with and seven women without PCOS (control); we added 17[beta]-estradiol (0.

Specific relation between abdominal obesity and early-phase hyperglycemia is modulated by hepatic insulin resistance in healthy older women.

Objective: To describe the impact of abdominal obesity and hepatic insulin resistance on phase-specific glycemic responses in older women.

Research Design And Methods: We studied 23 healthy older women (60-88 years old). Abdominal obesity was defined by an abdominal circumference > or =95 cm.

Simple exercise recovery index for sympathetic overactivity is linked to insulin resistance.

Unlabelled: Exercise HR recovery (HRR) has proven an effective clinical means to assess parasympathetic dysfunction linked to all-cause mortality, but an analogous functional assessment for sympathetic dysfunction has not been developed.

Purpose: We investigated whether exercise recovery provides additional cardiorespiratory information, beyond the initial HRR period, to index sympathetic overactivity associated with insulin resistance.

Methods: Young people (N = 20) with diverse percent body fat (9%-52%) were studied using fasting, oral glucose tolerance test (OGTT), and high-carbohydrate meal measurements.

Progressive improvement in glucose tolerance following lower-intensity resistance versus moderate-intensity aerobic training in older women.

Background: Few studies have compared long-term moderate-intensity aerobic versus light-resistance training on serial improvements in glucose tolerance in older people.

Methods: Healthy, inactive older (74 +/- 5 [SD] years) women (N = 20) were randomized into either a high-volume, moderate-intensity aerobic (ATM, n = 12) or a lower-intensity resistance training (RTL, n = 8) group. Both groups exercised under supervision 4 times per week for 45- to 60-min sessions over 9 months.

Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance.

Objective: Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT).

Methods: We therefore conducted a 4-month double-blind clinical trial in 28 obese [mean body mass index (BMI): 40.3 +/- 5.

Abdominal obesity in older women: potential role for disrupted fatty acid reesterification in insulin resistance.

Context: Excess abdominal adiposity is a primary factor for insulin resistance in older age.

Objectives: Our objectives were to examine the role of abdominal obesity on adipose tissue, hepatic, and peripheral insulin resistance in aging, and to examine impaired free fatty acid metabolism as a mechanism in these relations.

Design: This was a cross-sectional study.

Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat.

Background: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established.

Methods: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation.

Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training.

Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)).

The "obese insulin-sensitive" adolescent: importance of adiponectin and lipid partitioning.

There is a wide interindividual variation in peripheral insulin sensitivity at any given body mass index or percent body fat among obese adolescents with normal glucose tolerance. The goals of this study were to determine whether variability in insulin sensitivity is associated with differences in patterns of lipid partitioning or substrate use under fasting and hyperinsulinemic conditions. We compared 14 obese insulin-resistant adolescents with 14 obese insulin-sensitive controls, pair matched for age, gender, pubertal stage and body composition.

The normal glucose tolerance continuum in obese youth: evidence for impairment in beta-cell function independent of insulin resistance.

Normal glucose tolerance is expressed over a wide range of glucose concentrations. Whether there is a continuum of risk for developing type 2 diabetes mellitus even when the 2-h plasma glucose is still within this normal range is uncertain. Oral glucose tolerance tests were performed in 407 obese normal glucose tolerance youth (4-20 yr) to examine the relationship between variations in 2-h plasma glucose levels and beta-cell responsiveness.

Leg glucose and protein metabolism during an acute bout of resistance exercise in humans.

The present study investigated the responses of leg glucose and protein metabolism during an acute bout of resistance exercise. Seven subjects (5 men, 2 women) were studied at rest and during a strenuous lower body resistance exercise regimen consisting of approximately 8 sets of 10 repetitions of leg press at approximately 75% 1 repetition maximum and 8 sets of 8 repetitions of knee extensions at approximately 80% 1 repetition maximum. L-[ring-2H5]phenylalanine was infused throughout the study for measurement of phenylalanine rates of appearance, disappearance, protein synthesis, and protein breakdown across the leg.