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Biomedical subjects

J S Stern

Publications and source records attributed to J S Stern.

At least 73 records · Page 4Linked to original sources

Effects of dietary energy density and feeding frequency on total daily energy intakes of recovering malnourished children.

To develop recommendations for the design of special foods for young children, we measured total daily energy consumption from semisolid food mixtures with energy densities of 1.67, 2.93, 4.18, or 6.28 kJ/g (0.4, 0.7, 1.0, or 1.5 kcal/g) and that were fed ad libitum three, four, or five times per day to 18 fully weaned children from 6 to 18 mo of age who were recovering in the hospital from malnutrition. The diets were generally indistinguishable by sensory qualities, and were fed in a randomized sequence. The mean amounts consumed (g.kg body wt-1.d-1) were significantly less with successively greater energy density of the diet (P < 0.001). The total daily consumption was approximately 16% more when the number of meals was increased from three to four per day, with energy density controlled for (P < 0.001), and 7% more when the feeding frequency rose from four to five meals per day (P = 0.005). The total daily energy intakes (kJ.kg body wt-1.d-1) increased significantly with the more concentrated diets (P < 0.001) and varied positively in relation to feeding frequency (P < 0.001). Approximately 15-20 min were required per meal for the children to reach satiety. The total amount of time required to feed the children each day was related to the number of meals served (P < 0.001) and not to energy density. Implications for child feeding are discussed.

Defecation↗

A low protein diet lowers islet insulin secretion but does not alter hyperinsulinemia in obese Zucker (fa/fa) rats.

The effects of feeding a low protein diet on pancreatic insulin secretion early in life in genetically lean and obese Zucker rats were studied. Four-week-old lean (Fa/Fa) and obese (fa/fa) Zucker rats were fed either a 5% protein or a 20% protein diet for 3 wk. Rats were killed at 7 wk of age. Pancreatic islets were isolated and insulin response of islets was measured in a 60-min static incubation under one of the following conditions: 2.7 mmol/L glucose +/- 10 mmol/L arginine, 8.3 mmol/L glucose +/- 10 mmol/L arginine, and 16.7 mmol/L glucose. Serum insulin was significantly lower (P < or = 0.05) in lean, but not in obese rats fed low protein compared with those fed the normal protein diet. Interestingly, obese rats fed the low protein diet had the highest plasma glucose concentrations (P < or = 0.05) among the four groups. Feeding the low protein diet reduced insulin secretion of islets from lean rats by 70%, and from obese rats by 30 to 50% compared with rats fed the normal protein diet. Insulin content of islets was reduced significantly in lean rats fed the low protein diet (by 70%) and in obese rats (by 50%). A short-term protein deficiency early in life reduced in vitro insulin secretion of islets from both lean and obese rats. However, reductions in insulin content and insulin release from islets resulting from low protein feeding were not sufficient to alter hyperinsulinemia in genetically obese Zucker rats.

Animals↗

Chronic protein restriction does not alter energetic efficiency or brown adipose tissue thermogenic capacity in genetically obese (fa/fa) Zucker rats.

Attenuated regulatory thermogenesis in genetically obese (fa/fa) Zucker rats involves an impaired capacity to increase sympathetic drive to brown adipose tissue in response to dietary stimuli. Young, growing lean rats fed a low protein diet reduce energetic efficiency to compensate for elevated energy intake; however, it is not known if obese rats adapt similarly to chronic protein restriction by decreasing energetic efficiency and whether this would be accompanied by increased brown adipose tissue thermogenic capacity. Lean (Fa/Fa) and obese Zucker rats were either protein-restricted (protein 8% of total energy) or fed a control diet (21% protein) starting at age 5 wk. At 9 wk, oxygen consumption (VO2) was measured in response to an intubated meal of mixed macronutrient composition. Mass-adjusted food intake (i.e., food intake/body weight 0.67) was greater in protein-restricted than in control lean rats, but not different due to diet in obese rats. Mass-adjusted brown adipose tissue uncoupling protein levels were more than 100% greater in protein-restricted vs. control lean rats, but not different between protein-restricted and control obese rats. The uncoupling protein level was not significantly different in control lean vs. obese rats. Energetic efficiency was 40% lower in protein-restricted vs. control lean, but not different in obese rats; however, the efficiency of protein utilization was significantly greater in obese protein-restricted than in obese control rats. Meal-induced energy expenditure (VO2) did not differ significantly due to diet or genotype. In conclusion, protein restriction led to overfeeding in lean rats which appeared to enhance brown adipose tissue thermogenic capacity and decrease energetic efficiency. Protein efficiency increased to more than two times its original value in obese (fa/fa) rats, but otherwise no metabolic accommodation in the capacity for regulatory thermogenesis was observed in this genotype.

Adipose Tissue↗

Effect of insulin-like growth factor type 1 on critical-size defects in diabetic rats.

A number of investigators have reported on the clinically significant relationship between diabetes mellitus and impaired wound healing. Diabetic patients have an increased frequency of infection, delayed scar formation, and poor bony union. Investigations completed in our laboratory have demonstrated that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown promise for accelerating bony repair. The purpose of this study was to examine the effects of recombinant IGF-1 on standardized, critical-size calvarial defects in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes-induced rats.

Animals↗

Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocin-diabetic rats.

Glucagon response to insulin-induced hypoglycaemia is impared in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg(-1) min(-1) for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 micrograms kg(-1)) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg(-1) subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L(-1). As expected, the plasma glucagon response was reduced by approximately 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 +/- 92 pg mL(-1) in controls (P = 0.009) and by 570 +/- 137 pg mL(-1) in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 +/- 208 pg mL(-1) (P < 0.001) in controls but only by 555 +/- 242 pg mL(-1) in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impared by approximately 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impared concomitantly with the impared glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.

Animals↗

Weighing the options: criteria for evaluating weight-management programs. The Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity.

The United States is experiencing an epidemic of obesity among both adults and children. Approximately 35 percent of women and 31 percent of men age 20 and older are considered obese, as are about one-quarter of children and adolescents. While government health goals for the year 2000 call for no more than 20 percent of adults and 15 percent of adolescents to be obese, the prevalence of this often disabling disease is increasing rather than decreasing. Obesity, of course, is not increasing because people are consciously trying to gain weight. In fact, tens of millions of people in this country are dieting at any one time; they and many others are struggling to manage their weight to improve their appearance, feel better, and be healthier. Many programs and services exist to help individuals achieve weight control. But the limited studies paint a grim picture: those who complete weight-loss programs lose approximately 10 percent of their body weight, only to regain two-thirds of it back within 1 year and almost all of it back within 5 years. These figures point to the fact that obesity is one of the most pervasive public health problems in this country, a complex, multifactorial disease of appetite regulation and energy metabolism involving genetics, physiology, biochemistry, and the neurosciences, as well as environmental, psychosocial, and cultural factors. Unfortunately, the lay public and health-care providers, as well as insurance companies, often view it simply as a problem of willful misconduct--eating too much and exercising too little. Obesity is a remarkable disease in terms of the effort required by an individual for its management and the extent of discrimination its victims suffer. While people often wish to lose weight for the sake of their appearance, public health concerns about obesity relate to this disease's link to numerous chronic diseases that can lead to premature illness and death. The scientific evidence summarized in Chapter 2 suggests strongly that obese individuals who lose even relatively small amounts of weight are likely to decrease their blood pressure (and thereby the risk of hypertension), reduce abnormally high levels of blood glucose (associated with diabetes), bring blood concentrations of cholesterol and triglycerides (associated with cardiovascular disease) down to more desirable levels, reduce sleep apnea, decrease their risk of osteoarthritis of the weight-bearing joints and depression, and increase self-esteem. In many cases, the obese person who loses weight finds that an accompanying comorbidity is improved, its progression is slowed, or the symptoms disappear. Healthy weights are generally associated with a body mass index (BMI; a measure of whether weight is appropriate for height, measured in kg/m2) of 19-25 in those 19-34 years of age and 21-27 in those 35 years of age and older. Beyond these ranges, health risks increase as BMI increases. Health risks also increase with excess abdominal/visceral fat (as estimated by a waist-hip ratio [WHR] > 1.0 for males and > 0.8 for females), high blood pressure (> 140/90), dyslipidemias (total cholesterol and triglyceride concentrations of > 200 and > 225 mg/dl, respectively), non-insulin-dependent diabetes mellitus, and a family history of premature death due to cardiovascular disease (e.g., parent, grandparent, sibling, uncle, or aunt dying before age 50). Weight loss usually improves the management of obesity-related comorbidities or decreases the risks of their development. The high prevalence of obesity in the United States together with its link to numerous chronic diseases leads to the conclusion that this disease is responsible for a substantial proportion of total health-care costs. We estimate that today's health-care costs of obesity exceed $70 billion per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Weight↗

Characteristics of the obesity syndrome in Zucker-Brown Norway (ZBN) hybrid rats.

The existence of a restriction fragment length polymorphism (RFLP) closely linked to the fatty locus between the Zucker (Z) and Brown Norway (BN) rat strains allows evaluation of early effects of the fatty (fa) gene using offspring of back-crosses (N2) between F1 females and Zucker obese males. We examined several metabolic characteristics of N2 animals to determine if these hybrid animals exhibited similar characteristics of the obese syndrome to those of Zucker rats. Females from crosses of obese male Zucker (fa/fa) and lean female BN (+/+) rats were back-crossed to their sires, resulting in twelve N2 litters. At 9 weeks of age, liver, spleen, interscapular brown fat (IBAT), and gonadal, retroperitoneal (RP), and inguinal fat depots were removed and weighed. Samples of the RP depot were analyzed for cell size and number. Obese N2 rats were hyperphagic, with body weights in the range of those of obese Zucker rats. Obese N2 rats were also hyperinsulinemic [mean +/- SEM, microU/ml: females, 7.9 +/- 0.6 vs. 82.1 +/- 8.4 (lean vs. obese); males, 10.5 +/- 1.6 vs. 128.5 +/- 13.4 (lean vs. obese)] and mildly hyperglycemic [mean +/- SEM, mg/dl: females, 104.1 +/- 2.0 vs. 139.0 +/- 14.7 (lean vs. obese); males, 100.9 +/- 2.6 vs. 132.0 +/- 2.8 (lean vs. obese) p < or = 0.05]. White fat depots in obese rats were 3 to 7 times heavier than those in lean rats; adipocyte numbers in RP depots were 50% greater in obese than in lean rats; and cell size was more than 3 times larger. IBAT, liver, and spleen were also heavier in obese vs. lean rats, while tail lengths were shorter. Percent lean carcass mass and % carcass protein were about 30% greater in lean vs. obese rats, while % carcass fat in obese rats was 5 times greater than that of lean rats. Thus, phenotypic expression of the fa gene in ZBN hybrid animals, with approximately 25% of their genetic background coming from the BN strain, appears to be similar to that in Zucker rats. Given the similarity of phenotypic expression of the fa gene between the Zucker strain and ZBN hybrids, it is plausible to consider using ZBN hybrids for studies of early manifestations of fa gene action prior to onset of detectable obesity.

Adipocytes↗

Hypothalamic monoaminergic activity in 11-week-old cold-exposed female lean (Fa/Fa) and obese (fa/fa) Zucker rats.

We previously reported that serotonergic activity was reduced in the ventromedial hypothalamic nucleus (VMN) of obese vs. lean male Zucker rats. To verify that this reduction was associated with genotype rather than gender, we measured monoamines and their major metabolites in hypothalamic nuclei of 11-week-old female lean (Fa/Fa) and obese (fa/fa) Zucker rats. In addition, since the thermic response to cold is reported to differ between lean and obese rats, some rats were also exposed to 9 degrees or 22 degrees C for 2h to determine if cold exposure altered hypothalamic monoaminergic activity. As in males, levels of 5-hydroxyindoleacetic acid [5-HIAA; major metabolite of serotonin (5-HT)] and the ratio of 5-HIAA/5-HT were lower in the VMN of obese vs. lean females (P = 0.008, 0.001, respectively). 5-HIAA/5-HT was also reduced in the paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the obese compared to the lean females. Cold exposure significantly stimulated brown fat mitochondrial GDP binding in lean but not obese rats. Similarly, levels of norepinephrine, dopamine (DA), 5-HIAA, and 5-HT in the PVN, and 5-HIAA in the SCN increased in cold-exposed lean but not obese rats. In contrast, VMN and preoptic 3,4-dihydroxyphenylacetic acid (DOPAC; major metabolite of DA) increased in the cold-exposed obese but not lean animals. We conclude that: (1) the blunted peripheral response to cold in obese vs. lean Zucker rats is accompanied by altered hypothalamic monoaminergic activity, the physiological role of which needs further evaluation; and 2) depressed VMN serotonergic activity is associated with the obese genotype (fa/fa) rather than gender and as such may contribute to the reduced sympathetic and enhanced parasympathetic outflow from the VMN.

Adipose Tissue, Brown↗

The male obese Wistar diabetic fatty rat is a new model of extreme insulin resistance.

The male obese Wistar Diabetic Fatty (WDF) rat is a genetic model of obesity and non-insulin dependent diabetes (NIDDM). The obese Zucker rat shares the same gene for obesity on a different genetic background but is not diabetic. This study evaluated the degree of insulin resistance in both obese strains by examining the binding and post binding effects of muscle insulin receptors in obese rats exhibiting hyperinsulinemia and/or hyperglycemia. Insulin receptor binding and affinity and tyrosine kinase activity were measured in skeletal muscle from male WDF fa/fa (obese) and Fa/? (lean) and Zucker fa/fa (obese) and Fa/Fa (homozygous lean) rats. Rats were fed a high sucrose (68% of total Kcal) or Purina stock diet for 14 weeks. At 27 weeks of age, adipose depots were removed for adipose cellularity analysis and the biceps femoris muscle was removed for measurement of insulin binding and insulin-stimulated receptor kinase activity. Plasma glucose (13.9 vs. 8.4 mM) and insulin levels (14,754 vs. 7440 pmol/L) were significantly higher in WDF obese than in Zucker obese rats. Insulin receptor number and affinity and TK activity were unaffected by diet. Insulin receptor number was significantly reduced in obese WDF rats ( 2.778 +/- 0.617 pmol/mg protein), compared to obese Zucker rats (4.441 +/- 0.913 pmol/mg potein). Both obese strains exhibited down regulation of the insulin receptor compared to their lean controls. Maximal tyrosine kinase (TK) activity was significantly reduced in obese WDF rats (505 +/- 82 fmol/min/mg protein) compared to obese Zucker rats (1907 +/- 610 fmol/min/mg protein). Only obese WDF rats displayed a decrease in TK activity per receptor. These observations establish the obese WDF rat as an excellent model for exploring mechanisms of extreme insulin resistance, particularly post-receptor tyrosine kinase-associated defects, in non-insulin dependent diabetes.

Adiposity↗

Use of glycated hemoglobin to assess Glycemic control in Wistar diabetic fatty rats and Zucker fatty rats.

The Wistar Diabetic Fatty rat (WDF fafa) is a congenic strain of the Wistar Kyoto rat. Studies using blood glucose reveal that only fatty male (not female) WDF rats spontaneously develop hyperglycemia when fed a stock diet. Blood glucose values have not provided consistent results for evaluation of glycemic status in fatty male WDF rats. Zucker fatty (fafa) rats, while sharing the fa gene and the development of hyperinsulinemia and hyperlipemia, do not spontaneously become hyperglycemic. In order to examine strain differences and the effects of age on long-term average glycemic status in WDF and Zucker rats, glycated hemoglobin (GHb) was analyzed. Glycated hemoglobin was measured in male lean and obese WDF and Zucker rats at 2, 3, 6, and 12 months of age. Nonfasted plasma glucose was measured in male lean and obese WDF rats at 2, 3, 6, and 12 months of age and in lean and obese Zucker rats at 3, 6, and 12 months of age. Plasma insulin was measured in lean and obese WDF and Zucker rats at 3, 6, and 12 months of age. Obese WDF rats had significantly elevated GHb compared to lean controls at 3, 6, and 12 months of age. Glycated hemoglobin was substantially above the normal range (3.8-6.5%) at 3 months of age (14.1%). Glycated hemoglobin significantly declined in the obese WDF rats between 6 and 12 months of age. Nonfasted plasma glucose was significantly elevated in the obese WDF rats at 3 months (14.1 +/- 2.1 mM/L) and 6 months of age (16.2 +/- 2.3 mM/L) compared to lean controls. At 12 months of age there was no difference in plasma glucose between obese and lean WDF rats. Obese and lean Zucker rats had similar levels of GHb and plasma glucose at all ages. In conclusion, GHb provides more integrated data for classifying disease status of WDF rats and evaluation of potential long-term complications associated with hyperglycemia.

Age Factors↗

Rats on a macronutrient self-selection diet eat most meals from a single food cup.

Computerized meal pattern analysis was performed on female Sprague-Dawley rats (n = 10). Rats were housed for 14 days in cages adapted for macronutrient selection. Rats selected their diet from vitamin and mineral supplemented, semipurified sources of carbohydrate, fat and protein, in three individual food cups. For analysis of meal patterns, minimum meal size was > 50 mg, and mean minimum intermeal interval was 7.9 min. Daily energy intake averaged 289.0 kJ, with 75% occurring during the dark cycle. Energy intake was 28% carbohydrate, 50% fat and 22% protein. Of 12.3 daily meals, 56% were from one, 35% from two, and only 9% of the meals were from three food cups. Seventy percent of the time carbohydrate was the first meal of the dark cycle. The average number of meals per day eaten from carbohydrate, fat, and protein were not significantly different (6.9, 6.2 and 5.6, respectively, p > 0.05). Energy intake for a meal was greatest when fat was eaten (18.35 kJ), than when either carbohydrate (8.68 kJ) or protein (8.97 kJ) was eaten. Meal duration was 7.03 min for carbohydrate, 3.75 min for fat, and 7.47 min for protein. These results provide evidence that rats on a macronutrient self-selection diet eat most meals from a single macronutrient source.

Animals↗

Redundant parasympathetic and sympathoadrenal mediation of increased glucagon secretion during insulin-induced hypoglycemia in conscious rats.

Both the parasympathetic and sympathoadrenal inputs to the pancreas can stimulate glucagon release and are activated during hypoglycemia. However, blockade of only one branch of the autonomic nervous system may not reduce hypoglycemia-induced glucagon secretion, because the unblocked neural input is sufficient to mediate the glucagon response, ie, the neural inputs are redundant. Therefore, to determine if parasympathetic and sympathoadrenal activation redundantly mediate increased glucagon secretion during hypoglycemia, insulin was administered to conscious rats pretreated with a muscarinic antagonist (methylatropine, n = 7), combined alpha- and beta-adrenergic receptor blockade (tolazoline + propranolol, n = 5) or adrenergic blockade + methylatropine (n = 7). Insulin administration produced similar hypoglycemia in control and antagonist-treated rats (25 to 32 mg/dL). In control rats (n = 9), plasma immunoreactive glucagon (IRG) increased from a baseline level of 125 +/- 11 to 1,102 +/- 102 pg/mL during hypoglycemia (delta IRG = +977 +/- 98 pg/mL, P < .0005). The plasma IRG response was not significantly altered either by methylatropine (delta IRG = +677 +/- 141 pg/mL) or by adrenergic blockade (delta IRG = +1,374 +/- 314 pg/mL). However, the IRG response to hypoglycemia was reduced to 25% of the control value by the combination of adrenergic blockade + methylatropine (delta IRG = +250 +/- 83 pg/mL, P < .01 v control rats). These results suggest that the plasma glucagon response to hypoglycemia in conscious rats is predominantly the result of autonomic neural activation, and is redundantly mediated by the parasympathetic and sympathoadrenal divisions of the autonomic nervous system.

Adrenal Glands↗

Human subcutaneous adipose tissue shows site-specific differences in fatty acid composition.

Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose than in outer thigh (P < 0.002 for all); 16:1 and 18:1 omega 9 were lower in abdomen vs outer thigh (P < 0.01), whereas 18:1 omega 7 and 20:1 omega 9 were unchanged. Polyunsaturates 18:2 omega 6, 20:3 omega 6, and 20:4 omega 6 were higher in outer thigh than in abdomen (P < 0.06), and inner thigh values were intermediate. These changes in fatty acid composition resulted in lower mean triglyceride melting points from abdomen to inner thigh to outer thigh, and suggest that temperature may influence the selection process determining the variation in adipose fatty acid composition with anatomical location. Because the site-specific differences included essential fatty acids, selective uptake as well as potential differences in in situ fatty acid modification are indicated.

Abdomen↗

Serotonergic activity is depressed in the ventromedial hypothalamic nucleus of 12-day-old obese Zucker rats.

We previously reported lower ventromedial hypothalamic nucleus (VMN) serotonergic activity in 11-wk genetically obese vs. lean Zucker rats. To determine whether the activity was secondary to metabolic alterations associated with this established obesity (e.g., significant hyperphagia and hyperinsulinemia), we examined monoaminergic activity in various brain nuclei of 12-day lean (Fa/Fa and Fa/fa) and obese (fa/fa) rats early in the development of obesity. Obese pups had greater percent carcass fat than heterozygotes, both of which were fatter than homozygous lean rats. Obese, but not heterozygous lean, pups were hyperinsulinemic vs. Fa/Fa pups. VMN 5-hydroxy-3-indoleacetic acid levels, an index of serotonin release, were lower in obese and heterozygous than in homozygous lean pups and were not correlated with plasma insulin levels. Although monoamine differences also occurred in several other nuclei, for the most part they appeared to be unrelated to the obese genotype. We conclude that blunted VMN serotonergic activity is not secondary to the obese rat's hyperinsulinemia and may play a significant role in the development of obesity.

Adipose Tissue↗

Dietary macronutrient composition influences tissue trace element accumulation in diabetic Sprague-Dawley rats.

The purpose of the present investigation was to study the role of two potential contributory factors, hyperphagia and alterations in fuel metabolism, on the development of tissue trace element accumulation in the experimentally induced diabetic rat. The role of increased mineral intake associated with diabetic hyperphagia on tissue trace element accumulation was evaluated by feeding control and diabetic rats high-carbohydrate (HC) diets which varied in Zn, Cu, Mn, and Mg concentrations. Diabetic rats were hyperphagic and had lower plasma Mg, and higher liver Zn, Cu, and Mn concentrations than control rats, regardless of dietary mineral intake. In a second study, diabetic hyperphagia was reduced by feeding control and diabetic rats a HC, high-fat (HF), or high-protein (HP) diet; the effects of altering diabetic metabolism on trace element status was studied. Liver Mn and Zn concentrations of diabetic rats fed the HF diet were lower than diabetic rats fed the HC diet and HP diet, and were similar to control rats. Liver Cu concentrations of diabetic rats fed the HF and HP diets were lower than diabetic rats fed the HC diet and were similar to control rats. While diabetic rats, in general, had higher plasma glucagon concentrations and lower percent body fat than control rats, diabetic rats fed the HF diet had similar plasma glucagon and percent body fat to control rats. These data suggest that tissue-specific biochemical needs, such as the need for metals as cofactors for enzymes, rather than hyperphagia per se, may drive the accumulation of trace elements in the diabetic animal.

Animals↗

Exercise reduces fat selection in female Sprague-Dawley rats.

This study investigates the relationship between exercise and dietary macronutrient selection. Female Sprague-Dawley rats (5 months old) were placed on a macronutrient self-selection diet for 15 wk. Three food cups, each containing a separate vitamin and mineral supplemented macronutrient, i.e., fat, carbohydrate, or protein, were placed in the cage. Animals were either sedentary (Sed) or treadmill exercised (Ex) at 20 m.min-1, 60 min.d-1, for 6 d.wk-1. Cumulative daily energy and macronutrient intake were determined during this period. Energy intake was not different between Sed and Ex, 211.4 vs 213.5 kjoules.d-1, respectively. However, macronutrient intake differed with less fat eaten for Ex than Sed (81.5 kjoules and 38% for Ex; 114.0 kjoules and 47% for Sed). Carbohydrate and protein intake did not differ significantly between groups. Fifteen weeks of exercise training decreased dietary fat selection, but daily energy intake was not affected.

Animals↗

Altered alpha 1-adrenoceptor binding in intact and adrenalectomized obese Zucker rats (fa/fa).

While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean (Fa/Fa) and obese (fa/fa) male Zucker rats were assayed for alpha 1-([3H]prazosin; [3H]PRZ) and alpha 2-adrenoceptor ([3H]paraminoclonidine; [3H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [3H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding (Bmax) in obese rats was associated with decreased affinity (increased Kd). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [3H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [3H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (Bmax) associated with Adx were accompanied by decreases in Kd. Unlike [3H]PRZ binding, there was no consistent genotype difference in [3H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher alpha 2- to alpha 1-adrenoceptor ratio than lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Tonic sympathetic nervous system inhibition of insulin secretion is diminished in obese Zucker rats.

It has long been known that the central nervous system (CNS) directly affects pancreatic insulin release. This study was undertaken to determine the effect of the CNS on pancreatic insulin release in three-month-old female lean (Fa/Fa) and hyperinsulinemic obese (fa/fa) Zucker rats. Chloral hydrate (400 mg/kg) was used as the anesthetic agent. The in situ brain-pancreas perfusion model with intact pancreatic innervation was used in this investigation. The study measured insulin secretion in response to a 60-minute glucose stimulus (200 mg/dl). CNS-intact and CNS-functionally ablated obese and lean rats were used. During the 60-minute perfusion period significantly more insulin was released by pancreata from obese rats compared to those from lean rats. In lean rats, about twice as much insulin was released by pancreata from CNS-ablated rats than from CNS-intact rats (P < 0.05), demonstrating a CNS tonic inhibition of insulin secretion. In obese rats, there was no significant difference in insulin released by the pancreata of the CNS-intact and CNS-ablated rats. To determine if there was a masking effect of predominant PNS activity over the SNS in the CNS-intact obese rats, bilateral vagotomy was performed in a group of otherwise CNS-intact obese rats prior to the onset of perfusion. Tonic inhibition was still not observed in the CNS-vagotomized obese rats. In conclusion, hypersecretion of insulin in obese rats is partially due to diminished tonic sympathetic nervous system inhibition of insulin release. These results provide additional evidence regarding abnormal CNS control of insulin secretion in obese Zucker rats.

Analysis of Variance↗