Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst.

Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is "vigilant" and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst

Activation of Peroxisome Proliferator–Activated Receptor β/δ Inhibits Lipopolysaccharide-Induced Cytokine Production in Adipocytes by Lowering Nuclear Factor-κB Activity via Extracellular Signal–Related Kinase 1/2

OBJECTIVE—Chronic activation of the nuclear factor-κB (NF-κB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator–activated receptor (PPAR) β/δ activation prevents inflammation in adipocytes

Lipocalin-2 Deficiency Attenuates Insulin Resistance Associated With Aging and Obesity

OBJECTIVE - The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS - Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance-inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4- dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS - Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. © 2010 by the American Diabetes Association.link_to_OA_fulltex

Measuring body composition in overweight individuals by dual energy x-ray absorptiometry

BACKGROUND: Dual energy x-ray absorptiometry (DXA) is widely used for body composition measurements in normal-weight and overweight/obese individuals. The limitations of bone densitometers have been frequently addressed. However, the possible errors in assessing body composition in overweight individuals due to incorrect positioning or limitations of DXA to accurately assess both bone mineral density and body composition in obese individuals have not received much attention and are the focus of this report. DISCUSSION: We discuss proper ways of measuring overweight individuals and point to some studies where that might not have been the case. It appears that currently, the most prudent approach to assess body composition of large individuals who cannot fit under the scanning area would be to estimate regional fat, namely the regions of thigh and/or abdomen. Additionally, using two-half body scans, although time consuming, may provide a relatively accurate measurement of total body fat, however, more studies using this technique are needed to validate it. SUMMARY: Researchers using bone densitometers for body composition measurements need to have an understanding of its limitations in overweight individuals and address them appropriately when interpreting their results. Studies on accuracy and precision in measurements of both bone and soft tissue composition in overweight individuals using available densitometers are needed

Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.</p> <p>Methods</p> <p>We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.</p> <p>Results</p> <p>Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).</p> <p>Conclusion</p> <p>Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.</p

Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss

BackgroundMetabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured.Methodology and principal findingsForty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m(2)) participants were randomized to four groups for 6-months;Controlenergy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were -1.0+/-1.1% (CONTROL), -10.4+/-0.9% (CR), -10.0+/-0.8% (CR+EX) and -13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (-454+/-76 kcal/d) and LCD (-633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (-316+/-118 kcal/d) and LCD (-389+/-124 kcal/d) but reached significance only when CR and LCD were combined (-351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by -431+/-51 and -240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6.ConclusionsFor the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance.Trial registrationClinicalTrials.gov NCT00099151.Leanne M. Redman, Leonie K. Heilbronn, Corby K. Martin, Lilian de Jonge, Donald A. Williamson, James P. Delany, Eric Ravussin, for the Pennington CALERIE tea

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: A functional neuroimaging study

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.International Journal of Obesity advance online publicatio

Estimation of Activity Related Energy Expenditure and Resting Metabolic Rate in Freely Moving Mice from Indirect Calorimetry Data

Physical activity (PA) is a main determinant of total energy expenditure (TEE) and has been suggested to play a key role in body weight regulation. However, thus far it has been challenging to determine what part of the expended energy is due to activity in freely moving subjects. We developed a computational method to estimate activity related energy expenditure (AEE) and resting metabolic rate (RMR) in mice from activity and indirect calorimetry data. The method is based on penalised spline regression and takes the time dependency of the RMR into account. In addition, estimates of AEE and RMR are corrected for the regression dilution bias that results from inaccurate PA measurements. We evaluated the performance of our method based on 500 simulated metabolic chamber datasets and compared it to that of conventional methods. It was found that for a sample time of 10 minutes the penalised spline model estimated the time-dependent RMR with 1.7 times higher accuracy than the Kalman filter and with 2.7 times higher accuracy than linear regression. We assessed the applicability of our method on experimental data in a case study involving high fat diet fed male and female C57Bl/6J mice. We found that TEE in male mice was higher due to a difference in RMR while AEE levels were similar in both groups, even though female mice were more active. Interestingly, the higher activity did not result in a difference in AEE because female mice had a lower caloric cost of activity, which was likely due to their lower body weight. In conclusion, TEE decomposition by means of penalised spline regression provides robust estimates of the time-dependent AEE and RMR and can be applied to data generated with generic metabolic chamber and indirect calorimetry set-ups