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Biomedical subjects

Randy J Seeley

Publications and source records attributed to Randy J Seeley.

At least 19 recordsLinked to original sources
PubMed2007

Visceral abdominal fat is correlated with whole-body fat and physical activity among 8-y-old children at risk of obesity.

BACKGROUND: Abdominal fat is more related to health risk than is whole-body fat. Determining the factors related to children's visceral fat could result in interventions to improve child health. OBJECTIVE: Given the effects of physical activity on adults' visceral fat, it was hypothesized that, after accounting for whole-body fat, physical activity would be inversely related to children's visceral (VAT), but not to subcutaneous (SAT), abdominal adipose tissue. DESIGN: In this cross-sectional observational study conducted in forty-two 8-y-old children (21 boys, 21 girls) at risk of obesity [>75th body mass index (BMI) percentile, with at least one overweight parent], familial factors (eg, maternal BMI), historic weight-related factors (eg, birth weight), and the children's current physical activity (self-reported and measured with accelerometry) and diet were examined as potential correlates of the children's whole-body composition (measured with BMI and dual-energy X-ray absorptiometry) and abdominal fat distribution (measured by magnetic resonance imaging). RESULTS: Accelerometer-measured physical activity was related to whole-body fat (r = -0.32, P < 0.10), SAT (r = -0.29, P < 0.10), and VAT (r = -0.43, P < 0.05). In regression models, whole-body fat was positively associated with and the only significant correlate of SAT. Whole-body fat was positively related and accelerometer-measured physical activity was negatively and independently related to the children's VAT. CONCLUSIONS: Both SAT and VAT in 8-y-old children at risk of obesity are most closely associated with whole-body fat. However, after control for whole-body fat, greater physical activity is only associated with lower VAT, not SAT, in these children.

Absorptiometry, Photon↗
PubMed2006

Leptin in energy balance and reward: two faces of the same coin?

Leptin receptors are expressed on mesolimbic dopamine neurons, yet little is known about the functional significance of this anatomical relationship. In this issue of Neuron, Hommel et al. reveal a novel site for leptin's regulation of feeding. In turn, Fulton et al. propose a novel role for leptin in regulating non-feeding-related motivated behaviors.

Animals↗
PubMed2006

Role for dopamine-3 receptor in the hyperphagia of an unanticipated high-fat meal in rats.

Behavioral studies have indicated that midbrain dopamine projections arising in the ventral tegmental area and substantia nigra play a central role in integrating violations of expectancy in reward-related paradigms. The present study was designed to assess violations of dietary expectation and the role the dopamine-3 receptor plays in integrating reward-related food intake in violations of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3 h of access to food per day) in which they received either standard rodent chow or a preferable, high-fat diet. Animals either received the diet they had access to during the training period (no contrast) or the opposite diet (negative and positive contrast). As predicted, animals in the positive contrast condition were hyperphagic compared to no contrast animals. Animals in the negative contrast (high fat to chow) condition were hypophagic compared to no contrast animals. A dopamine agonist specific to the dopamine three receptor, ((+/-)-7-Hydroxy-dipropylaminotetralin HBr) and the dopamine-2 receptor antagonist raclopride were administered in equimolar doses peripherally to assess the involvement of the dopamine receptor subtypes in the violation of expectancy food intake effects. 7-Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with positive contrast and did not disrupt intake in the negative contrast or no contrast paradigm. Raclopride was ineffective at disrupting food intake. These results support the hypothesis that the dopamine-3 receptor is involved in the hyperphagia of an unexpected high fat meal.

Animals↗
PubMed2006

Hypothalamic mTOR signaling regulates food intake.

The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

Animals↗
PubMed2006

Effect of growth hormone on susceptibility to diet-induced obesity.

Mice with a deficiency in GH function due to disruption of the GH receptor/binding protein gene (GHR(-/-)) are long lived, insulin sensitive, and obese, whereas mice with excess GH function due to expression of a bovine GH transgene (bGH) are short lived, glucose intolerant, and lean. When challenged with a high-fat (HF) diet, we hypothesized that these mice would be differentially susceptible to diet-induced obesity. To test this hypothesis, GHR(-/-), bGH, and littermate control (WT) mice were fed a HF diet (40% kcal) or a nutrient-matched low-fat diet (9% kcal) for 12 wk. On the HF diet, all mice, regardless of genotype, showed a similar percent weight gain and exhibited a significant increase in percent body fat and the mass of epididymal, retroperitoneal, and sc fat pads. For bGH mice, the increase in adipose tissue was relatively small, compared with the WT or GHR(-/-) mice, suggesting some resiliency, although not immunity, to diet-induced obesity. GHR(-/-) mice, which are relatively obese on a low-fat diet, responded to the dietary challenge in a manner similar to WT controls. With HF feeding, all genotypes experienced an increase in insulin levels and depot-dependent effect of adipose tissue. Together, these results further support a role for GH in energy balance regulation and nutrient partitioning. More importantly, because there were genotype-specific effects of diet, these data stress the importance of diet selection and sampling multiple adipose depots in studies with these mouse models.

Animals↗
PubMed2006

Hap1 and GABA: thinking about food intake.

GABA stimulation of hypothalamic GABAA receptors increases food intake and body weight. Huntingtin-associated protein-1 (Hap1), is highly expressed in the hypothalamus and increases activity at GABAA receptors; mice lacking Hap1 are hypophagic. A recent paper (Sheng et al.,2006) further explores the role of Hap1 in the control of food intake.

Animals↗
PubMed2005

Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status.

Circulating levels of the orexigenic peptide ghrelin increase during fasting and decrease with refeeding. Exogenous ghrelin administration is a potent stimulus for food intake in rodents and humans. In subjects on fixed feeding schedules, ghrelin increases before each meal, raising the possibility that anticipation of meals, in addition to effects of fasting and feeding, contributes to ghrelin secretion. To distinguish among these regulatory influences, plasma ghrelin profiles were generated in freely fed rats and in meal-fed rats trained to consume their daily calories over a 4-h period in the light phase. In freely feeding rats, plasma ghrelin levels increased to a peak of 778 +/- 95 pg/ml just before the onset of the dark. Similarly, in meal-fed rats anticipating a large meal of either chow or Ensure at their usual feeding time, plasma ghrelin increased steadily over the 2 h preceding the meal to peaks of 2192 +/- 218 and 2075 +/- 92 pg/ml, respectively. When freely fed rats were food deprived for a time equivalent to meal-fed rats, there was no peak of plasma ghrelin. In addition, eating-induced suppression of the ghrelin response differed significantly between meal-fed rats and ad libitum-fed rats receiving meals of similar size. These findings indicate that anticipation of eating, as well as fasting/feeding status, influences pre- and postprandial plasma ghrelin levels in rats. Together, these data are consistent with a role for ghrelin in the regulation of anticipatory processes involved in food intake and nutrient disposition.

Animals↗
PubMed2005

Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating.

The purpose of this study was to determine the effect of chronic food restriction and reduced dietary fat on feeding behavior and body weight. Young female rats were fed ad lib or food restricted on a low-fat (LF) or a fat-free (FF) diet for 4 weeks. Rats then received 24-h free access to 2 diets, the maintenance diet (LF or FF) plus a novel high-fat (HF) diet (24-h intake test). After the test, all the rats were allowed chronic free access to the HF diet until body weight was stable. During the 24-h test, the restricted groups ate significantly more calories than the ad lib groups, and the FF-restricted rats ate significantly more total food, carbohydrate and protein than the LF-restricted rats; there were no differences between the two ad lib groups. During chronic free access to the HF diet, the formerly restricted rats achieved and defended lower body weights than the formerly non-restricted rats. Throughout the experiment, the ad lib groups had more body fat than the restricted groups independent of the dietary subgroup. Hence, a history of chronic food restriction predisposes to consuming more food in acute feeding situations, particularly when dietary fat is reduced, and lowers the level of body weight maintained and defended. Chronic food restriction accompanied by reduced dietary fat may increase risk for bouts of overeating.

Animals↗
PubMed2005

Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.

Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 microg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 microg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.

Animals↗
PubMed2005

Comparative analysis of ACTH and corticosterone sampling methods in rats.

A frequently debated question for studies involving the measurement of stress hormones in rodents is the optimal method for collecting blood with minimal stress to the animal. Some investigators prefer the implantation of indwelling catheters to allow for frequent sampling. Others argue that the implantation of a catheter creates a chronic stress to the animal that confounds stress hormone measures and therefore rely on tail vein sampling. Moreover, some investigators measure hormones in trunk blood samples obtained after anesthesia, a practice that may itself raise hormone levels. To address these controversies, we 1) compared plasma ACTH and corticosterone (Cort) concentrations in pre- and poststress rat blood samples obtained via previously implanted vena cava catheters, tail vein nicks, or clipping the tip off the tail and 2) compared plasma ACTH and Cort in rat blood samples obtained by decapitation with and without anesthesia. Rats sampled via indwelling catheters displayed lower prestress ACTH levels than those sampled by tail vein nick if the time to acquire samples was not limited; however, elevated basal ACTH was not observed in samples obtained by tail clip or tail nick when the samples were obtained within 3 min. Baseline Cort levels were similar in all groups. After restraint stress, the profile of the plasma ACTH and Cort responses was not affected by sampling method. Decapitation with prior administration of CO2 or pentobarbital sodium increased plasma ACTH levels approximately 13- and 2-fold, respectively, when compared with decapitation without anesthesia. These data indicate that tail vein nicking, tail clipping, or indwelling venous catheters can be used for obtaining plasma for ACTH and Cort during acute stress studies without confounding the measurements. However, the elevation in basal ACTH seen in the tail vein nick group at baseline suggests that sampling needs to be completed rapidly (<3 min) to avoid the initiation of the pituitary stress response. Death by CO2 and pentobarbital sodium injection before trunk blood collection cause significant stress to animals, as reflected in the elevated plasma ACTH levels. These results support the use of either chronic vascular cannulas or sampling from a tail vein. However, collection of blood under pentobarbital sodium or CO2 anesthesia is likely to confound the results of stress studies when ACTH is an important endpoint.

Adrenocorticotropic Hormone↗
PubMed2005

The effect of the melanocortin agonist, MT-II, on the defended level of body adiposity.

A wide range of experimental evidence implicates a critical role for melanocortin signaling in the control of food intake and body adiposity. Melanocortin receptor agonists such as MT-II potently reduce food intake and body weight, making such agonists potential therapeutics for obesity. The critical concept addressed by the present experiments is whether the homeostatic effects of melanocortin agonists directly regulate food intake or whether the effects on food intake are secondary, with the primary effects being the regulation of body weight and adiposity. To investigate this, we compared the effect of various doses of MT-II given via osmotic minipump for 28 d to alter food intake, body weight, and body fat in dietary-induced obese rats. In addition, before the implantation of the minipump, dietary-induced obese rats were weight reduced by differing amounts using varying levels of food restriction. The results show that in food-restricted rats, MT-II-treated rats consume significantly more calories than those receiving MT-II after ad libitum access to food. More importantly, regardless of the widely differing levels of body fat among the different dietary treatments employed, body fat at the end of the study was determined exclusively by the dose of MT-II, with MT-II-treated rats having less body fat than vehicle-treated rats. These experiments support the hypothesis that melanocortin signaling primarily regulates total body adiposity and that food intake is adjusted as necessary to achieve a specific level of body adiposity.

Adipose Tissue↗
PubMed2005

Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity.

Oleoylethanolamide (OEA), a lipid synthesized in the intestine, reduces food intake and stimulates lipolysis through peroxisome proliferator-activated receptor-alpha. OEA also activates transient receptor potential vanilloid type 1 (TRPV1) in vitro. Because the anorexigenic effect of OEA is associated with delayed feeding onset and reduced locomotion, we examined whether intraperitoneal administration of OEA results in nonspecific behavioral effects that contribute to the anorexia in rats. Moreover, we determined whether circulating levels of other gut hormones are modulated by OEA and whether CCK is involved in OEA-induced anorexia. Our results indicate that OEA reduces food intake without causing a conditioned taste aversion or reducing sodium appetite. It also failed to induce a conditioned place aversion. However, OEA induced changes in posture and reduced spontaneous activity in the open field. This likely underlies the reduced heat expenditure and sodium consumption observed after OEA injection, which disappeared within 1 h. The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-alpha agonist Wy-14643. Plasma levels of ghrelin, peptide YY, glucagon-like peptide 1, and apolipoprotein A-IV were not changed by OEA. Finally, antagonism of CCK-1 receptors did not affect OEA-induced anorexia. These results suggest that OEA suppresses feeding without causing visceral illness and that neither ghrelin, peptide YY, glucagon-like peptide 1, apolipoprotein A-IV, nor CCK plays a critical role in this effect. Despite that OEA-induced anorexia is unlikely to be due to impaired motor activity, our data raise a cautionary note in how specific behavioral and metabolic effects of OEA should be interpreted.

Animals↗
PubMed2005

Neuropeptide Y prepares rats for scheduled feeding.

When neuropeptide Y (NPY) is administered centrally, meal-anticipatory responses are elicited. If an increase of endogenous NPY is a signal that heralds an imminent large caloric load, timed daily NPY injections may be expected to condition meal-anticipatory responses that facilitate ingestion. Rats received 4-h access to food beginning in the morning and then timed (1600 h), daily third-ventricular injections of NPY or saline for 7 days. On test day (day 8), animals received the conditioning drug (NPY or saline) or the opposite drug. Food was available immediately after injection on test day, and intake was measured. Rats conditioned with NPY and then given saline ate significantly more than rats conditioned with saline and then given saline; they ate the same amount as rats given NPY. Although they ate more, rats trained with NPY did not have changed plasma glucose, insulin, or ghrelin. These data suggest that NPY plays a role in mediating conditionable food-anticipatory responses that help to cope with the effects of large caloric loads.

Animals↗
PubMed2005

Diet-induced weight loss is associated with decreases in plasma serum amyloid a and C-reactive protein independent of dietary macronutrient composition in obese subjects.

Elevated levels of serum amyloid A (SAA) and C-reactive protein (CRP) have been associated with increased cardiovascular risk. Although levels of CRP decrease with weight loss, it is not known whether SAA decreases with weight loss or whether dietary macronutrient composition affects levels of either SAA or CRP. SAA and CRP levels were measured retrospectively on baseline and 3-month plasma samples from 41 obese (mean body mass index 33.63 +/- 1.86 kg/m2) women completing a randomized trial comparing a low-fat diet (n = 19) and a very low-carbohydrate diet (n = 22). For the 41 participants, there were significant decreases from baseline to 3 months in both LogSAA (P = 0.049) and LogCRP (P = 0.035). The very low-carbohydrate dieters had a significantly greater decrease in LogSAA (P = 0.04), but their weight loss also was significantly greater (-7.6 +/- 3.2 vs. -4.3 +/- 3.5 kg, P < 0.01). In this study, the decreases in inflammatory markers correlated significantly with weight loss (r = 0.44, P = 0.004 vs. LogSAA and r = 0.35, P = 0.03 vs. LogCRP). Also, change in LogSAA correlated with change in insulin resistance (r = 0.35, P = 0.03). Thus, in otherwise healthy, obese women, weight loss was associated with significant decreases in both SAA and CRP. These effects were proportional to the amount of weight lost but independent of dietary macronutrient composition.

Blood Pressure↗
PubMed2005

The role of previous exposure in the appetitive and consummatory effects of orexigenic neuropeptides.

The ingestion of foods is comprised of two distinct phases of behavior: appetitive and consummatory. While most food intake paradigms include both phases, the intraoral intake test emphasizes the stereotyped consummatory-phase by infusing a liquid food directly into the oral cavity. Several hypothalamic peptides have been shown to increase intake of chow in standard food intake paradigms and the current experiments sought to test whether these peptides would increase food intake in the intraoral intake paradigm. NPY, melanin-concentrating hormone (MCH) and orexin-A were infused into the third ventricle (i3vt) in a counterbalanced latin-square design just prior to rats getting 0.1M sucrose solution infused via indwelling intraoral catheters and compared it to intake on bottle tests with access to the same sucrose solution. On the first day, each peptide increased intraoral intake relative to saline in the between-subjects comparison. Moreover, intake of sucrose following i3vt saline increased as a function of training. By the final day of the experiment, rats receiving saline consumed as much sucrose as rats receiving NPY, MCH, or orexin-A. This finding was conceptually replicated in the second experiment in which rats drank sucrose freely from a bottle on the home cage. A third experiment directly assessed the role of previous exposure in the sucrose intake induced by NPY. Those results confirm that repeated exposure to sucrose increases baseline intake and attenuates the hyperphagic effect of NPY. These results are consistent with two conclusions: (1) NPY, MCH, and orexin-A increase both appetitive and consummatory-phase ingestive behaviors on initial exposures; (2) repeated training interacts with the effects of these orexigenic peptides.

Administration, Oral↗