Biomedical subjects

D B West

Publications and source records attributed to D B West.

At least 37 records · Page 2Linked to original sources

PubMed1998

Dietary fat, genetic predisposition, and obesity: lessons from animal models.

This review focuses on animal studies that examine the role of dietary fat in obesity. It is evident from animal experiments that the percentage of energy derived from fat in the diet is positively correlated with body fat content. With few exceptions, obesity is induced by high-fat diets in monkeys, dogs, pigs, hamsters, squirrels, rats, and mice. The mechanisms responsible for this correlation between body fat and dietary fat content are not clear. It has been proposed that a high-fat diet produces hyperphagia, which is solely responsible for the increased body fat content. However, several studies in various rodent models showed that increased body fat content still results when the hyperphagia is prevented. This suggests that some metabolic effects of high-fat diets, independent of hyperphagia, may also be contributing to the obesity induced by high-fat diets. It is also clear from animal studies that genetic factors significantly modulate the body's response to diets high in fat-derived energy. In contrast with the animal studies, studies in humans that have examined the relation between dietary fat content and body fat are inconclusive. The limitations of cross-sectional studies, the lack of controlled feeding trials, and the importance of genetic variation in response explain the absence of conclusive evidence. The lessons learned from animal models point to dietary fat as one potentially important component in the etiology of human obesity. Additional comprehensive studies are warranted to determine the role of dietary fat in the etiology of human obesity.

Adipose Tissue↗

PubMed1998

Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in the fat of beef and other ruminants. CLA is reported to have effects on both tumor development and body fat in animal models. To further characterize the metabolic effects of CLA, male AKR/J mice were fed a high-fat (45 kcal%) or low-fat (15 kcal%) diet with or without CLA (2.46 mg/kcal; 1.2 and 1.0% by weight in high- and low-fat diets, respectively) for 6 wk. CLA significantly reduced energy intake, growth rate, adipose depot weight, and carcass lipid and protein content independent of diet composition. Overall, the reduction of adipose depot weight ranged from 43 to 88%, with the retroperitoneal depot most sensitive to CLA. CLA significantly increased metabolic rate and decreased the nighttime respiratory quotient. These findings demonstrate that CLA reduces body fat by several mechanisms, including a reduced energy intake, increased metabolic rate, and a shift in the nocturnal fuel mix.

Adipose Tissue↗

PubMed1997

Inherited non-autosomal effects on body fat in F2 mice derived from an AKR/J x SWR/J cross.

In this study we describe the contribution of matrilineal and patrilineal effects on the adiposity, body weight, and on the weights of individual fat pads in F2 male mice derived from an SWR/J x AKR/J cross. AKR/J mice become obese after 12 weeks on a high-fat diet, whereas SWR/J mice remain relatively lean. Here we report that mice with AKR maternal and AKR paternal grandmothers have significantly larger epidydimal and retroperitoneal fat pads than those with SWR maternal and paternal grandmothers. However, grandparental strain had no effect on the overall adiposity (AI) or the weights of the inguinal, subcutaneous or mesenteric fat pads. The strain of the paternal grandparents had a small but significant effect on body weight. These effects can be attributed to in utero effects, imprinting effects, cytoplasmic and/or Y chromosome transmission of factors controlling body fat. We also describe the presence of a quantitative trait locus (QTL) on Chromosome X, close to DXMit174, which is linked to adiposity, body weight, and to the weights of the individual fat depots. However, this QTL is not responsible for the grandparental strain effects described above.

Adipose Tissue↗

PubMed1997

Carbohydrate versus fat intake: differing patterns of macronutrient selection in two inbred mouse strains.

As a first step toward developing a mouse model to characterize genetic factors linked to the preferential intake of dietary carbohydrate or fat, we have identified two mouse strains that exhibit distinctly different patterns of macronutrient selection. Macronutrient selection was evaluated in AKR/J and SWR/J mice, two strains that have been characterized previously for their sensitivity to high-fat dietary obesity. Mice were adapted to a self-selection protocol in which separate carbohydrate, fat, and protein sources were simultaneously available. AKR/J mice ate 30% more calories than the SWR/J mice. Furthermore, strain comparisons revealed a significantly higher proportion of fat intake by the AKR/J mice (69 vs. 28%), and in the SWR/J mice a significantly higher intake of carbohydrate (62 vs. 24%). The mice were then returned to a standard chow diet for 10 wk. These mice subsequently were allowed to self-select from two composite energy diets (carbohydrate and protein, or fat and protein). Once again, AKR/J mice selected a greater proportion of energy from the fat/protein diet (85%) than did the SWR/J strain (32%). These findings suggest a possible relationship between sensitivity to dietary obesity and fat selection.

Animal Nutritional Physiological Phenomena↗

PubMed1996

Differential metabolic effects of energy restriction in dogs using diets varying in fat and fiber content.

The role of dietary fat and fiber in energy restriction for the management of obesity was examined. Twelve male castrated dogs were energy restricted for 7 weeks by feeding 60% of their calculated maintenance energy requirements (MER = 1500 kcal/m2/d) for ideal body weight. Six dogs were restricted on a high-fat (35.4 kcal% from fat), low-fiber (2.9% dry matter basis [DMB]) diet while the other six dogs were restricted on a low-fat (24.5 kcal% from fat), high-fiber (27% DMB) diet. Compared with the high-fat, low-fiber diet, energy restriction on the low-fat, high-fiber diet resulted in significantly greater decreases in body fat (1472 +/- 166 vs. 853 +/- 176 g; p < 0.05) and total serum cholesterol concentrations (108.7 +/- 11.3 vs. 51.5 +/- 13.9 mg/dL; p < 0.005). Reductions in body weight (2.86 +/- 0.3 vs. 2.14 +/- 0.3 kg; p < 0.09), and mean arterial blood pressure (17.4 +/- 6.1 vs. 6.7 +/- 2.9 mmHg; p < 0.12) were also greater on the low-fat diet; however, these diet effects did not reach statistical significance. These data suggest that the fat and fiber content of the diet during energy restriction are important factors in the management of obesity.

Adipose Tissue↗

PubMed1996

Sensitivity to dietary obesity linked to a locus on chromosome 15 in a CAST/Ei x C57BL/6J F2 intercross.

Details of a new model of diet-dependent polygenic obesity are presented. CAST/Ei (Mus m. castaneus) mice remain lean after 12 weeks on a high-fat (32 kcal% fat) diet, while C57BL/6J mice become obese. The genes responsible for the obesity segregate in an F2 population derived from an intercross between CAST/Ei and C57BL/6J mice. Quantitative trait analysis, with simple sequence length polymorphisms (SSLPs) at loci previously linked to rodent obesities, identified a quantitative trait locus (QTL) on Chromosome (Chr) 15, accounting for approximately 9% of the variance in adiposity and 14% of the variance in mesenteric depot size. This locus appears to be at the same location as the dietary obesity-3 (Do3) locus controlling body fat content, which was previously identified in an F2 population derived from an SWR/J x AKR/J cross. This is also at the same location as the multigenic obesity-4 (Mob4) locus found in BSB mice, which display spontaneous polygenic obesity. Suggestive linkage also was found at loci close to the single gene mutations Ay on Chr 2 and tub on Chr 7.

Adipose Tissue↗

PubMed1996

Genetics of obesity in humans and animal models.

Human obesity has a significant genetic component which contributes to the risk for this disorder. The application of molecular genetic techniques to identify these genes using a variety of approaches, including information from animal models, will help clarify the role of specific genes in the etiology of human obesity. Identification of these genetic mechanisms is likely to lead to new approaches, both pharmacologic and nonpharmacologic, for the prevention and treatment of this disease.

Animals↗

PubMed1996

Autonomic control of blood pressure and heart rate in obese hypertensive dogs.

Autonomic control of cardiovascular function was evaluated in nine dogs before and after a high-fat overfeeding regimen. Body weight increased significantly (from 19.8 +/- 0.9 to 29.5 +/- 2.1 kg; P < 0.01) with overfeeding. Mean arterial pressure (MAP) increased from 94.6 +/- 2.1 to 105.5 +/- 3.7 mmHg (P < 0.05), and heart rate (HR) increased from 94.8 +/- 3.5 to 112.3 +/- 5.6 beats/min (P < 0.01). After ganglionic blockade with chlorisondamine, dose response of MAP and HR to methoxamine (alpha-agonist) or isoproterenol (beta-agonist) was evaluated. Peak MAP response to methoxamine was blunted in obese dogs. HR response to isoproterenol was not different between lean and obese dogs. Atropine in the presence of propranolol increased HR from 80.8 +/- 7 to 202.8 +/- 8.9 beats/min in lean dogs and from 113.8 +/- 12.1 to 131.7 +/- 18.2 in obese dogs. These data suggest the increase in HR observed in obese dogs may be due to a decrease in parasympathetic inhibition rather than an increase in sympathetic stimulation. The blunted response to methoxamine in obese hypertensive dogs suggests that the sympathetic control of peripheral vascular resistance is altered in obesity.

Animals↗

PubMed1996

Race and physical activity: cardiovascular and renal response to sodium loading.

Race and level of physical activity may be important factors affecting cardiovascular responsiveness to acute sodium intake. We examined the effects of a 4-day sodium loading procedure on heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, 24-hour electrolyte excretion, and extracellular fluid volume (ECF) in African-American (n = 16) and Caucasian (n = 16) adult males. All subjects were normotensive with either moderately high (> or = 3 day/wk; > or = 20 min/day) or low (< or = 3 day/wk; < or = 20 min/day) physical activity levels. Subjects ingested either placebo or NaCl (0.2 g/kg/day) during two 4-day periods. Sodium loading increased SBP and decreased HR in all high physical activity subjects but not in low physical activity subjects (p < 0.05). Na+ excretion did not differ among groups, although urine volume and K+ excretion were lower, and Na+/K+ excretion ratio was higher in African-American compared to Caucasian subjects (p < 0.05). ECF, as measured by NaBr dilution, was greater in high physical activity subjects compared to low physical activity subjects (p < 0.05). These data suggest that high physical activity levels do not attenuate but rather exaggerate SBP response to a sodium load.

Adult↗

PubMed1995

Dietary obesity in the mouse: interaction of strain with diet composition.

The effect of varying dietary macronutrient content on the body composition of AKR/J and SWR/J mice was examined. Dietary fat was fed at three levels (45, 30, and 15 kcal%), while dietary protein also was varied across three levels (10, 20, and 30 kcal%). All mice were placed on the defined diets at 5 wk of age and maintained on these diets for 12 wk. AKR/J mice were significantly larger and had a significantly greater carcass fat content compared with SWR/J mice in all dietary conditions. There was a clear dose-response effect of dietary fat on body fat in the AKR/J mice. In contrast, SWR/J mice showed an increase of body fat only when fed the diet containing the highest level of dietary fat and the lowest protein concentration. High levels of dietary protein (30 kcal%) resulted in a significant decrease of carcass fat in the AKR/J mice compared with diets containing either 20 or 10 kcal% protein. This effect of protein was not observed in the SWR/J mice except in the groups fed the 45 kcal% fat diets. These findings demonstrate a strong interaction of genetic background and macronutrient content of the diet on body composition. The AKR/J strain of mouse has a greater percentage of carcass fat and is more responsive to the effects of dietary fat composition compared with the SWR/J strain.

Adipose Tissue↗

PubMed1995

Validation of a radiotelemetry system for continuous blood pressure and heart rate monitoring in dogs.

A blood pressure telemetry system with catheter placement in the femoral artery was evaluated over a 119-day period in eight mongrel dogs. Every 3 weeks, the pressures recorded by telemetry were compared with direct, simultaneously recorded blood pressures measured from a femoral artery catheter implanted on the contralateral side. One telemetry device failed within 1 week of implant and was replaced before the beginning of data collection. Continuous blood pressure measures were accurate for a minimum of 17 weeks in all eight dogs. Acute changes in blood pressure and heart rate were not evaluated. Validation by simultaneous recording with a physiological monitor indicated that there was no drift in the telemetry blood pressure or heart rate during the 17-week period. Heart rates recorded by telemetry and a physiological monitor were identical, as were mean arterial pressures. The systolic pressure measured by the physiological monitor was consistently higher than that measured by telemetry. This may have been due to differences in the compliance of the catheter material in the two systems. Two devices failed within approximately 6 months of implant, apparently because of exhaustion of the battery. These findings indicate that this telemetry device can be used for periods of up to 17 weeks without appreciable drift or attenuation of the blood pressure signal. The results also describe a validation procedure for monitoring the accuracy of the telemetry system over extended periods of use. We conclude that this telemetry device can be used for the long-term assessment of blood pressure and heart rate in the dog.

Animals↗

PubMed1994

Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4.

We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1.

Alleles↗

PubMed1994

Insulin sensitivity of adipocytes from inbred mouse strains resistant or sensitive to diet-induced obesity.

We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content.

Adipocytes↗

PubMed1994

Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model.

Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice. AKR/J mice are sensitive to dietary obesity when fed a high fat diet while SWR/J mice are resistant. Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity. Using an F2 mapping population of 931 male mice we found significant linkage with a QTL on chromosome 9 (Likelihood of the Odds [LOD] ratio of 4.85) and another QTL on chromosome 15 (LOD = 3.93). The presence of a QTL on chromosome 15 was confirmed in a separate mapping population of 375 male F1 x SWR/J mice (LOD = 3.82). These two loci are designated dietary obese 2 (Do2) and dietary obese 3 (Do3) for the chromosome 9 and 15 loci, respectively. Both of these chromosomal regions contain candidate genes which may contribute to variation in the phenotype. These loci also exert a significant control over individual adipose depot weights.

Adipose Tissue↗

PubMed1993

Decreased potency of contraction to alpha-adrenoceptor stimulation in renal arteries from obese hypertensive dogs.

The contractile potencies of the alpha-adrenoceptor agonist phenylephrine (PhE) and two nonadrenergic vasoconstrictors, prostaglandin F2 alpha (PGF2 alpha) and endothelin, were evaluated in renal arterial muscle strips isolated from obese hypertensive (OH) dogs. Responses were compared with those obtained from renal arteries isolated from lean normotensive (LN) dogs. Identical dose-response curves were produced by PGF2 alpha in arteries from OH and LN dogs. This was also true for endothelin. However, the vasoconstrictor potency of PhE for arteries from OH dogs was approximately 2.5-fold less than that for arteries from LN dogs. This difference was not dependent on endothelial integrity. Although they were less potent to PhE, arteries from OH dogs did not produce weaker maximum contractile responses than arteries from LN dogs; responses produced by maximum K+ depolarization (S(o)) were approximately 2 x 10(5) N/m2, and responses to the maximally effective concentrations of PhE, PGF2 alpha, and endothelin were approximately 0.97-, 0.50-, and 0.87-fold S(o), respectively. In addition to the rightward shift in contractile potency to PhE, arteries from OH dogs precontracted with a maximum PhE concentration relaxed more to a high nitroglycerin concentration than did arteries from LN dogs. At a PhE concentration that produced equivalent maximum force responses, arteries from OH dogs had a lower rate of muscle shortening than did arteries from LN dogs, suggesting reduced cross-bridge activation in the arteries from OH dogs. These data suggest that alpha-adrenoceptor-induced activation was selectively downregulated in renal arteries from OH dogs.

Animals↗

PubMed1992

Early-onset repeated dieting reduces food intake and body weight but not adiposity in dietary-obese female rats.

As dieting behavior and attempts at weight loss are becoming increasingly common in adolescent girls, we wished to determine whether early-onset repeated dieting influenced the development of obesity and its metabolic correlates. Female rats were fed a high-fat diet and subjected to six cycles of dieting and regain, beginning in the peripubertal period. Although dieted rats weighted less than nondieted high-fat fed controls at the completion of the sixth cycle, body composition analysis revealed that the two groups were equally obese. Cumulative caloric intake was less in dieted rats, suggesting that the pattern of consumption promoted by dieting helped to establish the obesity. Resting metabolic rate did not differ between the two groups. These data suggest that although early-onset repeated dieting may result in reduced body weight, the eventual level of adiposity may be unknowingly elevated, potentially leading to long-term health risks.

Adipose Tissue↗

PubMed1992

Dietary obesity in nine inbred mouse strains.

The effect of 7 wk consumption of a diet containing 32.6% of kilocalories as fat [condensed milk (CM) diet] on body composition and energy intake was evaluated in nine strains of inbred mice (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, C57BL/6J, SJL/J, I/STN, and SWR/J). Control animals were fed a high-carbohydrate diet containing 11.6% of energy as fat (Purina Rodent Chow diet). Relative to Chow diet controls, the CM diet significantly increased carcass lipid content in six strains (AKR/J, C57L/J, A/J, C3H/HeJ, DBA/2J, and C57BL/6J), but had no or a marginal effect on adiposity in three strains of mice (SJL/J, I/STN, and SWR/J). The obesity produced by the CM diet in six strains was not due to hyperphagia. Only one of six (AKR/J) of the strains that increased adiposity on the CM diet consumed more energy than controls during the 7 wk of the experiment. The identification of inbred mouse strains that are sensitive to dietary obesity, vs. others that are resistant, provides a useful tool to pursue the metabolic and genetic basis of this trait in the mouse.

Animal Feed↗

PubMed1992

Blunted natriuretic response to an acute sodium load in obese hypertensive dogs.

Several studies support the premise that there is a strong relation between obesity and high blood pressure. Although the mechanism for obesity-related hypertension has not yet been fully elucidated, recent studies have suggested that abnormalities in renal sodium handling may be involved in the pathogenesis of obesity-induced hypertension. The purpose of the present study was to determine the effects of an acute saline load on renal excretory function in dogs with obesity-induced hypertension and in normotensive lean dogs. Experiments were performed in two groups of conscious, chronically instrumented dogs. One group of dogs (obese) was fed a high-fat diet for 5-6 weeks, and the other group (lean) ate a normal diet. The body weight of the obese dog group (26.3 +/- 0.7 kg) was 45% higher than the lean dog group (18.1 +/- 0.3 kg). Mean arterial pressure averaged 126 +/- 2 mm Hg in the obese dogs and 100 +/- 1 mm Hg in the lean dogs. The lean dogs had an average heart rate of 104 +/- 7 beats per minute, whereas the obese dogs averaged 134 +/- 8 beats per minute. Plasma renin activity was also significantly higher in the obese dogs. Both groups of dogs were given 135 meq sodium chloride over 60 minutes via an intravenous infusion of isotonic saline. Sodium and water excretion increased significantly in response to the acute saline load. However, the natriuresis and diuresis was markedly attenuated in the obese hypertensive dogs. During the first 40 minutes of saline loading, the increase in sodium and water excretion was 50-70% lower in the obese hypertensive dogs. The results of the present study indicate that obese hypertensive dogs have a reduced capability to excrete an acute sodium load. This abnormality in renal sodium handling may play a role in the pathogenesis of obesity-induced hypertension.

Animals↗