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D R Reed

Publications and source records attributed to D R Reed.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses.

Individual variability in sucrose consumption is prominent in humans and other species. To investigate the genetic contribution to this complex behavior, we conducted behavioral, electrophysiological, and genetic studies, using male progeny of two inbred mouse strains (C57BL/6ByJ [B6] and 129/J [129]) and their F2 hybrids. Two loci on Chromosome (Chr) 4 were responsible for over 50% of the genetic variability in sucrose intake. These loci apparently modulated intake by altering peripheral neural responses to sucrose. One locus affected the response threshold, whereas the other affected the response magnitude. These findings suggest that the majority of difference in sucrose intake between male B6 and 129 mice is due to polymorphisms of two genes that influence receptor or peripheral nervous system activity.

Animals↗
PubMed1997

Heritable variation in food preferences and their contribution to obesity.

What an animal chooses to eat can either induce or retard the development of obesity; this review summarizes what is known about the genetic determinants of nutrient selection and its impact on obesity in humans and rodents. The selection of macronutrients in the diet appears to be, in part, heritable. Genes that mediate the consumption of sweet-tasting carbohydrate sources have been mapped and are being isolated and characterized. Excessive dietary fat intake is strongly tied to obesity, and several studies suggest that a preference for fat and the resulting obesity are partially genetically determined. Identifying genes involved in the excess consumption of dietary fat will be an important key to our understanding of the genetic disposition toward common dietary obesity.

Animals↗
PubMed1997

Familial risk ratios for extreme obesity: implications for mapping human obesity genes.

OBJECTIVE: To determine familial risk ratios for extreme obesity to aid in the design of obesity linkage studies. DESIGN: Family study of obesity. SUBJECTS: 2349 first-degree relatives (parents and siblings) of 840 probands who are members of the National Association to Advance Fat Acceptance (NAAFA) and 5851 participants of the first phase of the National Health and Nutrition Examination Survey III. METHODS: Computed age-gender standardized risk ratios (SRRs) for obesity in relatives categorized by the level of obesity in the index case (proband). MEASUREMENT: Body mass index (BMI) (kg/m2). RESULTS: The risk of extreme obesity (BMI > or = 40) in relatives of extremely obese women (BMI > or = 40) was more than five times greater than in the population; furthermore, the risk of obesity in relatives was approximately linearly associated with the degree of obesity in the proband. The risk of thinness in relatives of obese individuals was substantially lower than in the general population. CONCLUSION: Because the familial risk ratio for extreme obesity is higher than for moderate levels of obesity, the number of families required to achieve adequate statistical power in gene mapping studies of obesity can be reduced substantially by focusing on family members of extremely obese individuals (BMI > or = 40).

Adult↗
PubMed1996

Intake of ethanol, sodium chloride, sucrose, citric acid, and quinine hydrochloride solutions by mice: a genetic analysis.

Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F1 and F2 hybrids were offered solutions of ethanol, sucrose, citric acid, quinine hydrochloride, and NaCl in two-bottle choice tests. Consistent with earlier work, the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride solution and less NaCl solution than did 129 mice. Analyses of each generation's means and distributions showed that intakes of ethanol, quinine, sucrose, and NaCl were influenced by a few genes. The mode of inheritance was additive in the case of ethanol and quinine, for sucrose the genotype of the 129 strain was recessive, and for NaCl it was dominant. Citric acid intake appeared to be influenced by many genes with small effects, with the 129 genotype dominant. Correlations of sucrose consumption with ethanol and citric acid consumption were found among mice of the F2 generation, and the genetically determined component of these correlations was stronger than the component related to environmental factors. The genetically determined correlation between sucrose and ethanol intakes is consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component.

Alcohol Drinking↗
PubMed1996

Extreme obesity may be linked to markers flanking the human OB gene.

Mice with mutations of the ob gene are extremely obese, and the human homologue (OB) has been cloned and physically mapped. The protein product of the ob gene (leptin) reduces body fat in mice when given exogenously, and leptin has been proposed to provide a lipostatic signal that regulates adiposity. Variation in the OB gene may be one genetically determined cause of obesity in human populations. To test this hypothesis, we genotyped siblings from 78 families at markers flanking the human OB gene. Pairs of siblings with extreme obesity (BMI > or = 40; n = 59) shared haplotypes identical-by-descent for the region containing the OB gene at greater than chance levels (corrected P = 0.04). Furthermore, one haplotype containing the OB gene was transmitted by heterozygous parents to extremely obese (BMI > or = 40) offspring more frequently than expected by chance, indicting significant allelic disequilibrium (corrected P = 0.027). One explanation for these linkage findings is that some individuals with extreme obesity have an allelic variant of the OB gene, although other nearby genes could contribute to obesity in these families.

Adipose Tissue↗
PubMed1995

Absence of linkage between human obesity and the mouse agouti homologous region (20q11.2) or other markers spanning chromosome 20q.

Mutant alleles of the agouti gene cause obesity in the mouse and the homologous gene in humans has been mapped to chromosome 20q11.2. An allelic variant of the agouti gene could account for obesity in humans and we tested this hypothesis by genotyping 210 sibling pairs from 45 families segregating an obesity phenotype. Using sibling pair linear regression analysis, evidence for linkage between obesity and markers flanking the agouti locus and other markers spanning chromosome 20q was assessed. We found no correlation between identity-by-descent at these markers and obesity differences within pairs. In the mouse, obesity caused by mutations of the agouti gene develops later in life, so a subset of families with adult-onset obesity were also tested for linkage, with negative results. Although it is not possible to exclude alleles of the agouti gene as a contributor to obesity in humans, the absence of positive linkage in this study suggests that either the agouti gene has small effects or the allele frequency is low.

Age of Onset↗
PubMed1995

Propylthiouracil tasting: determination of underlying threshold distributions using maximum likelihood.

The ability to taste low concentrations of propylthiouracil (PROP) and related bitter compounds is heritable. The current analysis determines whether the distribution of PROP taste thresholds is consistent with an additive or a dominant mode of Mendelian transmission. To that end, the lowest concentration of PROP detectable was determined for 1015 subjects and models of bi- or tri-modal distributions of PROP taste thresholds were tested. The model with the greatest likelihood had three distributions and followed an additive model of PROP taste sensitivity if the variances associated with the distributions were assumed to be equal. However, if the taste thresholds were transformed to remove skewness, or if the variances were unequal, then three- or two-distribution models were equally likely. Resolution of the mode of inheritance for bitter taste perception awaits additional family studies and the characterization of the molecular basis of taste perception for these bitter compounds.

Adolescent↗
PubMed1995

Human obesity does not segregate with the chromosomal regions of Prader-Willi, Bardet-Biedl, Cohen, Borjeson or Wilson-Turner syndromes.

Prader-Willi, Bardet-Biedl, Cohen, Borjeson and Wilson-Turner syndromes are genetic disorders characterized by obesity and other diverse abnormalities. These disorders have been mapped to their respective chromosomal regions, and we hypothesize that each region contains a gene or genes important in the regulation of body weight. We tested this hypothesis by genotyping sibling pairs (n = 207; 17 markers) from 44 families who were segregating an extreme obesity phenotype but were otherwise clinically normal. The number of alleles shared between siblings from these chromosomal regions did not correlate with similarity in body mass index (kg/m2). If genes in these regions contribute to non-syndromal obesity, the prevalence is low and the corresponding alleles are rare.

Adult↗
PubMed1993

Obesity in families of extremely obese women.

In order to assess the prevalence of obesity in families of extremely obese individuals, we conducted a mail survey of a national obesity organization. Thirty-nine percent (N=981) of the questionnaires were completed and returned. Respondents were excluded from further analysis if they were adopted, male, their gender could not be determined, provided incomplete information about their parents or their own height and weight, or were less than 22 or greater than 63 years of age. The analyses included 729 probands and their families. Both the prevalence and the extent of obesity were high in the families members. The average family members' body mass index (BMI=kg/m2) was 30, and 78% of the families studied had at least one other obese (BMI>30 kg/m2) first-degree relative (parent, sibling, or child). Although obesity was common in the families, survey respondents were generally the heaviest members of their families, having an average BMI of 47 kg/m2. Correlations among first-degree relatives were similar to those found for average weight groups, suggesting that obesity and BMI are similarly influenced by family genetic factors in this extremely obese population.

Adult↗
PubMed1992

Experience with a macronutrient source influences subsequent macronutrient selection.

We examined the influence of experience with a macronutrient on subsequent macronutrient selection. For 4 days, rats ate chow, or chow and a single macronutrient source. They then had simultaneous access to protein, carbohydrate (CHO) and fat sources, according to a standard macronutrient self-selection paradigm. When selecting among the macronutrient sources, rats pre-exposed to CHO ate more CHO, and those pre-exposed to fat ate more fat, relative to the other groups. Rats pre-exposed to protein ate more protein than did those pre-exposed to CHO or fat but not more than those that received no macronutrient pre-exposure. These selection patterns persisted for at least 12 days, when the test was ended because of the low protein intakes and poor growth of the rats pre-exposed to the CHO and fat sources. After 34 days of recovery with only chow to eat, the rats were again allowed to choose among the three macronutrients, and their patterns of selection were essentially unchanged. Similar results were found in a second experiment in which a 5-day interval was interposed between macronutrient pre-exposure and macronutrient selection. These findings show that experience with the macronutrients typically used in self-selection experiments can have a large, long-lasting, and sometimes detrimental effect on subsequent food selection by rats. Prior experience can be a more powerful influence than nutritional wisdom in determining the rat's food choice.

Animals↗
PubMed1991

Sham-feeding sucrose or corn oil stimulates food intake in rats.

In separate experiments, rats with open gastric cannulas were sham-fed either 32% sucrose solution or 15% corn oil emulsion. The rats' cannulas were then closed, and food intake was measured for 2 h. Food intake was greater after sham-feeding either fluid than after tests when no fluid was available. These results suggest that the oral stimulation produced by ingestion of sweet or oily fluids can stimulate appetite in the rat.

Administration, Oral↗
PubMed1991

Enhanced acceptance and metabolism of fats by rats fed a high-fat diet.

Rats fed a high-fat diet show greater acceptance of and preference for pure fats than do rats fed a high-carbohydrate diet. We tested the hypothesis that this differential intake of fat was due to diet-induced modifications of lipid absorption and oxidation. After an intragastric load of corn oil, rats adapted to a high-fat diet had greater increases in plasma triglyceride and ketone levels and a lower percentage of fecal fat than did rats adapted to an isocaloric high-carbohydrate diet. High-fat-fed rats given corn oil containing [14C]palmitic acid expired 14CO2 more rapidly and to a greater extent than did rats maintained on a high-carbohydrate diet. These results show that the greater acceptance of fat by rats fed a high-fat diet is associated with an increased capacity to absorb and oxidize fat.

Animals↗
PubMed1990

Sham-feeding of corn oil by rats: sensory and postingestive factors.

Previous research indicates that rats fed a high-fat (HF) diet increase their intake and preference for oil compared with rats fed a high-carbohydrate (HC) diet. To assess whether this increased intake was due to the sensory or postingestive properties of oil, rats were adapted to either the HF or HC diet and then allowed to sham-feed pure corn oil daily for 30 min. During the first 4 trials, rats fed the HF diet sham-fed more oil than did rats fed the HC diet; however, this difference diminished with repeated testing and was absent after 8 trials. In both diet groups, 4-5 calories (approximately 25%) of sham-fed oil could not be recovered and may have escaped to the intestine. These results suggest that, compared with rats fed a HC diet, rats fed a HF diet are initially attracted to the sensory properties of oil, but that the differential oil intakes of rats fed the HF or HC diet are maintained by postingestive, rather than sensory factors.

Animals↗
PubMed1990

Diet composition alters the acceptance of fat by rats.

The acceptance of dietary fat by rats is influenced by changes in fat digestion and metabolism. In these experiments, rats were fed diets that differed in fat, carbohydrate and fiber content, and the acceptance of fat was measured. Rats fed a high fat (HF) diet ate more corn oil in 30-min or 6-h tests than did rats fed an isocaloric high carbohydrate (HC) diet. This effect was seen after the diets were switched and rats retested. Differences in dietary fiber between the isocaloric HF and HC diets did not account for this effect because rats fed HF diets, either high or low in fiber content, drank more oil than rats fed the HC diet. Rats fed the HF diet with added carbohydrate drank less oil than rats fed the HF diet, and the same amount of oil as rats fed the HC diet. Compared with rats fed the HC diet, rats fed the HF diet drank more oil in a two-bottle preference test with sucrose or when mixed with sucrose in a single-bottle test. Rats offered a variety of fats, sugars or other test foods, ate more nutritive liquid fats and some solid fats, but did not eat more sugar or other items if they were fed the HF diet rather than the HC diet. These studies taken together strongly suggest that rats fed a high fat diet show a greater acceptance of fat compared with rats fed a high carbohydrate diet.

Animals↗
PubMed1988

Weight cycling in female rats increases dietary fat selection and adiposity.

The effect of repeated food restriction-refeeding (weight cycling) on macronutrient selection and adiposity was investigated in female Sprague-Dawley rats. Rats were maintained on ad lib macronutrient self-selection and were put on one of two types of restriction. One group was reduced to 75% of their body weight on restricted amounts of chow and a second group was given ad lib chow during the concurrent period and were voluntarily hypophagic. During refeeding on macronutrient self-selection, animals previously restricted selected a higher percentage of dietary fat, had larger adipose depots and plasma insulin values, and had lower heart weights both expressed in grams and as a percentage of body weight than non-restricted groups. This suggests that both severe and moderate periods of restriction may have negative health consequences.

Animals↗