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Biomedical subjects

J A Grinker

Publications and source records attributed to J A Grinker.

At least 19 recordsLinked to original sources

Changes in patterns of fatness in adult men in relation to serum indices of cardiovascular risk: the Normative Aging Study.

BACKGROUND: Overweight and/or excessive weight gain, as well as changes in central fat deposition, have been implicated in increased incidence of coronary disease and type 2 diabetes. OBJECTIVE: We related adiposity (BMI, kg/m2, and waist circumference, WC, cm) to biochemical risk factors (cholesterol, triglyceride and glucose concentrations) for cardiovascular disease and diabetes. DESIGN: Associations were examined both cross-sectionally and longitudinally, among 867 men enrolled in the Normative Aging Study (NAS). We included all participants with complete anthropometric and clinical data at both enrollment (average age 45 y) and after approximately 15 y of follow-up (average age 60 y). We used multiple linear regression analysis to test relationships between body fatness and change in body fatness and the biochemical indices. RESULTS: In adulthood, concurrent BMI and waist circumference related significantly to triglyceride and glucose concentrations and to 2 h glucose responses at two time points. Measures of fatness 15 y earlier were also predictive of later triglyceride and glucose measures. When included together, BMI, but not WC, remained independently associated with triglycerides at both time points, while WC, but not BMI, remained significantly associated with fasting glucose concentrations and glucose response at the follow-up observation. In contrast, gains in weight and abdominal fat from entry to follow-up related more strongly to serum cholesterol concentrations than did concurrent measures. CONCLUSION: Attained weight, weight gain, and location of weight contribute differentially to these indices of cardiovascular and diabetes risk.

Adult↗

Overweight and leanness in adulthood: prospective study of male participants in the Normative Aging Study.

OBJECTIVE: Our objective was to examine the stability of body habitus over 15 years in Boston area adult males enrolled in the Normative Aging Study (NAS) and to examine stability as a function of initial leanness or obesity, age and reported body habitus at age 18. DESIGN: Prospective observational study of anthropometric/clinical measures initiated in 1961-1970, follow-up examinations at regular three and five year intervals. Subjects with complete data at entry, 5, 10 and 15 years. SUBJECTS: The 2280 Boston area subjects were aged 21-80 years (mean = 42 y) at entry. A subset (n = 350) with complete data for weight (WT) and height (HT) at four points over 15 years provided estimates of body habitus continuity. The prevalence of obesity and age of those studied were comparable to the complete sample of enrolled men (n = 1403) with any missing follow-up measures. MEASUREMENTS: Obesity was defined as body mass index (BMI) (weight in kg/height in m2) > or = 27.8 and leanness as BMI < 24.0. Three age categories at baseline (young = 25-39 y; middle = 40-49 y and old = 50-74 y) were used to examine secular and longitudinal changes. Obesity prevalence rates during late adolescence, based on self-reported weights at age 18, were compared with measured prevalence rates at entry and follow-up. Individual changes in BMI over time for each subject were estimated by linear regression and were combined to measure change in age and BMI groups. RESULTS: Weights and BMI at entry were highly correlated with 18 year values and 15 year follow-up values. New cases of obesity, defined on the basis of BMI, increased over time while the numbers of subjects classified as lean and intermediate decreased. Among oldest subjects both the lean and obese had slight but significant decreases in mean BMI. Among the lean, only the young showed consistent increments. DISCUSSION: Our results suggest consistency in body habitus among young and middle-aged obese subjects. There was little evidence of long-term reduction. In agreement with previous observations, the current findings of long-term duration in obesity suggest that preventive efforts should be focused on early years.

Adult↗

Weight gain by middle-aged mice: dietary modification does not result in loss.

Dietary induced obesity susceptibility and persistence was examined in middle aged female retired C57BL/6J breeder mice. One year old mice were fed control chow (C), chow with added corn oil (O), or chow with added sweetened condensed milk (SCM) for 18 weeks, during which time food consumption and weight change were monitored. Mice in both the O and SCM groups gained significantly more weight than the C group. Weight increase correlated with caloric intake for the O and SCM groups. All mice were then fed standard laboratory chow for 22 weeks. The increased weight of both supplemented groups was maintained during this time suggesting that caloric intake is not the sole variable controlling weight maintenance in adult female mice. We encourage the use of older mice as a model to explore means of manipulating adult weight in humans.

Adipose Tissue↗

Body habitus changes among adult males from the normative aging study: relations to aging, smoking history and alcohol intake.

The Normative Aging Study (NAS) recruited 2280 Boston area healthy males aged 21 to 80 in 1961 through 1970. Clinical exams have continued at 3- to 5-year intervals. Obesity was not an exclusion criterion. Stability in weight and body habitus among 867 adult participants in the NAS was evaluated at 5- and 15-year follow-ups. At study entry, age was linearly related to central adiposity [abdominal circumference (AC) and ratio of AC/Hip Breadth (HB)] throughout the entire age range (30 to 78 years) and linearly and quadratically related to weight (WT) and Body Mass Index (BMI) (kg/m2) with maximal values at age 50. Over 15 years, changes in adiposity were strongly related to age; the greatest increases were among those initially 30 to 44 years of age with decrements in several adiposity measures (BMI, AC) only among the oldest subjects (60+ at entry); significant quadratic effects of age for BMI (p < .001), WT (p < .02) and AC (p < .01). There were major secular differences; men born later were heavier and fatter at the same ages as men born earlier. Men who gained (> 1 BMI) were younger while men who lost (> 1 BMI) had greater initial central adiposity than others. Smoking cessation was independently associated with increments in both central and peripheral adiposity. Moderate alcohol intake was associated with lower gains in AC/HB ratios at 15 years compared with little or high consumption. In general, aging was associated with trends towards central adiposity which tended to plateau or decrease at the oldest ages.

Adult↗

Learned control of meal size in spontaneously obese and nonobese bonnet macaque monkeys.

Ten pairs of obese and nonobese monkeys, matched for age and sex, received one liquid test meal a day for 4 days. Testing was conducted during the middle of a 6-h period of food deprivation. At all other times the monkeys were freely fed on maintenance chow biscuits. The first test meal of grape and orange flavor drinks familiarized them with fluids containing an intermediate level of added carbohydrate (CHO) (27.5%); equal volumes of grape and orange flavors were presented. During testing, the positions of the two flavors were switched three times, thus forcing the monkey to make four choices during the meal. On days 2 and 3, four pairs of monkeys received low-energy liquid meals (10% CHO), and six pairs received high-energy meals (45% CHO); half of the pairs in each group had orange flavor, half grape. On day 2, meal volumes did not differ between the 10% and 45% CHO groups; rather, the size of the meal (regardless of CHO composition) correlated with mean daily chow intake. On day 3, the volume consumed of the 10% CHO solution increased and the volume of the 45% CHO solution decreased, generating a difference between groups that indicated one-trial learning of control of meal size. On day 4, each monkey was given a test meal of repeated choices between samples of grape and orange flavor, both containing the intermediate 27.5% CHO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clonidine hyperphagia: neuroanatomic substrates and specific function.

Recent studies have indicated that the alpha 2-noradrenergic agonist clonidine (CLON), when peripherally and centrally administered, potentiates feeding in satiated rats in a manner similar to that observed following injection of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN). The present experiments examined the effects of CLON on meal patterns and macronutrient selection and compared these findings to earlier NE-stimulated feeding studies. Administration of CLON (25 nmoles), directly into the PVN (n = 5), similar to PVN injected NE, produced an increase in meal size (190%) and feeding duration (164%), with no change in meal frequency. Additional tests were conducted in rats with PVN electrolytic or 6-hydroxydopamine lesions. In Sham rats (n = 16) peripheral CLON (0.05 mg/kg), like NE, produced an increase in food intake and particularly potentiated carbohydrate ingestion. Discrete electrolytic lesions of the PVN (n = 5) abolished this CLON-induced feeding and carbohydrate preference, suggesting that the PVN may be a primary site for CLON-stimulated hyperphagia. Neurotoxin lesions of the PVN (n = 17), which reduced PVN NE levels by 75%, failed to alter peripheral CLON-induced feeding. This and other evidence indicates that this agonist may be acting via postsynaptic alpha 2 receptors in the PVN to potentiate carbohydrate intake, rather than via presynaptic release of NE from nerve endings in the PVN.

Animals↗

Hypothalamic serotonin in the control of meal patterns and macronutrient selection.

Serotonin (5-HT) is believed to have an inhibitory influence over feeding behavior. The present experiments were designed to investigate the effects of hypothalamic 5-HT on spontaneously motivated feeding and appetite regulation. Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer. Following PVN 5-HT or NORFENF injection, animals exhibited a marked suppression in food intake, associated with a decrease in meal size, duration and eating rate, and no change in the frequency of meals consumed. This suggests that brain 5-HT may influence primarily the induction of satiety rather than the suppression of hunger. The effect of drugs presumed to affect brain 5-HT transmission on diet selection was also investigated in groups of rats injected centrally with 5-HT or NORFENF or peripherally with either fenfluramine, quipazine or cyproheptadine. In a series of 2-diet tests, rats centrally injected with 5-HT or NORFENF exhibited a selective suppression of the carbohydrate-rich diets. In animals provided with three pure macronutrient diets, protein, carbohydrate, and fat, systemic administration of serotonergic agents had its greatest impact on fat and carbohydrate ingestion, as compared to protein consumption. These findings support a role for hypothalamic 5-HT in modulating meal patterns and appetite for particular macronutrients.

Animals↗

Amphetamine: effects on meal patterns and macronutrient selection.

Catecholaminergic systems, specifically in the region of the lateral perifornical hypothalamus (PFH), have been linked to the inhibition of feeding behavior. The present studies examined the effects of d-amphetamine (AMPH), which is believed to act through the release of endogenous catecholamines (CAs), on spontaneous feeding and appetite regulation in rats. Injection of AMPH directly into the PFH caused a marked suppression of food intake; changes in computer-monitored meal patterns were characterized by an increase in the latency to meal onset and a consequent reduction in meal size and duration. This suggests that hypothalamic AMPH administration may influence primarily the initiation, rather than the termination, of feeding. In other experiments, chronic infusion of AMPH directly into the PFH was shown to suppress 24 hr food intake and body weight gain, indicating the effectiveness of lateral hypothalamic CA stimulation in overriding normal long-term patterns of feeding. The effect of hypothalamic CA stimulation on macronutrient selection was also investigated in groups of rats injected either centrally or peripherally with AMPH, or centrally with the CA agonists, dopamine and epinephrine. Each of these manipulations caused a strong inhibition of protein intake with no effect on carbohydrate, and only a mild suppression of fat ingestion after peripheral AMPH. These selective effects of AMPH on feeding patterns and diet choice, provide support for a role of CA innervation to the lateral hypothalamus in the modulation of natural feeding behavior and macronutrient selection.

Animals↗

Role of hypothalamic norepinephrine in control of meal patterns.

Feeding behavior has been shown to be strongly affected by central administration of catecholamines. In this study, we examined in freely-feeding rats the effect of hypothalamic norepinephrine (NE) injections on the basic parameters of spontaneous ingestion. Precise changes in feeding behavior in rats maintained on ad lib food and water intake were monitored by a PDP 8 computer connected to an apparatus capable of measuring licks and bites of food. Injections of NE were administered into the hypothalamic paraventricular nucleus, the most sensitive brain area for the elicitation of feeding through direct alpha-noradrenergic stimulation. In tests conducted under both light and dark conditions, NE facilitated food intake, primarily by an increase in meal size rather than meal frequency. The first meal after injection was increased in size and duration; the rate of eating was also enhanced. Whereas the following intermeal interval was significantly larger, subsequent meals and intermeal intervals appeared generally unaffected. This evidence is consistent with the proposal of a role for hypothalamic NE in the maintenance, rather than initiation, of feeding behavior in freely-feeding rats.

Animals↗

Effects of inhibitors of carbohydrate absorption or lipid metabolism on meal patterns of Zucker rats.

Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis (Ro 22-0654). All drugs were presented as diet admixtures over 3 or 4 consecutive days. Total food and water intakes, the temporal pattern of feeding, and the average meal frequency and meal size were measured using computerized data collection procedures. Inhibitors of carbohydrate absorption failed to suppress food intake in either obese or lean Zucker rats and had no effect on the parameters of feeding. In contrast, inhibitors of lipid metabolism reduced food intake by 56-77% by reducing both meal frequency and meal size. Direct inhibition of lipid metabolism may be a viable mechanism for anti-obesity agents.

Acarbose↗

Meal-taking behavior is related to predisposition to dietary obesity in the rat.

The hypothesis that early nutritional experience can determine endogenous patterns of meal-taking behavior and thereby affect predisposition to dietary obesity was tested by raising male Sprague-Dawley rats in litters of 4, 8, and 20, and examining their meal patterns and responsiveness to a high-fat, high-sugar (HFS) diet in adulthood. At 9 months of age, half the rats from each litter size group were given the HFS diet for 16 weeks, while the other half were continued on laboratory chow. As expected, HFS-fed rats gained more weight and developed larger fat depots and more and larger fat cells than did chow-fed controls. Analysis of meal-taking behavior just prior to the introduction of HFS-feeding allowed some of the rats to be classified as "gorgers" or "nibblers" according to their average daily meal size. While on lab chow, gorgers and nibblers showed no differences in body weight gain, but upon being switched to the HFS diet, gorgers gained significantly more weight than did nibblers, and showed a greater degree of fat depot enlargement. These findings suggest that patterns of meal-taking behavior can predict the magnitude of and may contribute to the development of dietary obesity.

Adipose Tissue↗

Dietary self-selection and meal patterns of obese and lean Zucker rats.

Following two weeks of baseline measures on laboratory chow, young obese and lean male Zucker rats were given access to separate macronutrients for 18 weeks. First, the rats were given access to soybean meal, dextrinized starch, and lard for eight weeks. Daily caloric intake of obese rats was greater on laboratory chow than that of lean rats and remained so following the switch to the self-selection diet. While obese and lean rats consumed similar proportions of each macronutrient over the eight-week period, there were substantial changes in the pattern of intake across weeks. Obese rats decreased daily caloric intake primarily by decreasing lard consumption. In contrast, lean rats maintained daily caloric intake while increasing the proportion of calories from fat. The addition of a 25% sucrose solution (weeks 11-18) produced an elevated daily caloric intake for both obese and lean rats, achieved through an increased carbohydrate intake with a simultaneous decrease in fat intake. A diurnal pattern of intake was maintained for each macronutrient. Compared to controls, rats on the self-selection diet did not show differential growth. Measurement of daily meal patterns for soybean meal, sucrose, and lard during the last four days of the experiment showed that obese rats ate significantly larger meals comprised of all three food components than did lean rats. For both obese and lean rats, one-component meals were primarily sucrose with greater intake during the light period. Lean rats showed a greater tendency to indulge in these between-meal "snacks" than did obese rats. These data suggest that palatability and nutrient source as well as length of exposure are critical determiners of nutrient selection and total daily caloric intake.

Animals↗

Body size estimation and locus of control in obese adolescent boys undergoing weight reduction.

Body size estimation (BSE) and locus of control (LOC) were studied in 18 obese adolescent boys undergoing weight reduction. The subjects attended a seven-week summer camp which offered both increased activity and a 1200 kcal (5023 kJ)/d diet, resulting in an average weight loss of 29.2 +/- 6.3 lb (13.3 +/- 2.9 kg) and a decrease in body fat from 39.0 percent +/- 0.6 percent to 27.5 percent +/- 4.3 percent. Fatness was correlated with poor physical performance [1.5 mile (2.4 km) runs]. Weight reduction and decreased body fat resulted in an improved running time. BSE was assessed using self photographs distorted by an anamorphic lens. While subjects could correctly estimate their body size prior to weight reduction, after weight reduction they significantly underestimated body size. This finding contrasts with adults with juvenile-onset obesity who overestimate body size after weight reduction. LOC (measured by Nowicki-Strickland LOC Inventory) changed in the direction of internality after weight reduction. The use of exercise with the weight loss program may thus improve feelings of control and prevent overestimation of body size.

Adolescent↗

Interrelationships among activity, food intake and weight gain in genetically obese and lean Zucker rats.

In Experiment 1, food deprivation resulting in a 30% reduction in body weight produced significant increases in wheel running in both obese and lean female Zucker rats. In Experiment 2, a new technique, food contingent activity (FR, VI), dramatically increased wheel running in both obese and lean female Zucker rats. This increase in activity was achieved primarily during the dark period. Regardless of changes in activity levels, food intake and body weight gain remained similar to controls. When food was again available ad lib, activity levels rapidly decreased for obese but not lean rats. These results indicate that behavioral interventions alone are not sufficient to correct the obesity of the genetically obese rat.

Animals↗

Cholecystokinin antibody injected in cerebral ventricles stimulates feeding in sheep.

The role of brain cholecystokinin peptides in satiety was further assessed by using antibody to cholecystokinin to reduce cholecystokinin activity in the cerebrospinal fluid of sheep. Food intakes were increased approximately 100 percent during the 2-hour continuous injection of antibody into the cerebrospinal fluid. This supports the hypothesis that, during feeding, cholecystokinin is released into the cerebrospinal fluid, which transports it to the receptors that elicit satiety.

Animals↗