Codominant effects of the fatty (fa) gene during early development of obesity

Truett, Gary E.; Tempelman, R. J.; Walker, Jerilyn A.

doi:10.1152/ajpendo.1995.268.1.e15

Cited by 16 publications

(27 citation statements)

References 11 publications

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“…The factor "sex" was not found to influence body mass growth significantly (P ϭ 0.42) of either MSG-treated or control pups. Least square means obtained by ANOVA of body mass measurements on day 10 showed for the controls that, in line with previous studies (18,38), average body mass of the females tended to be smaller (19.6 Ϯ 0.6 g) than that of the males (20.7 Ϯ 0.7), but MSG treatment reduced average body masses to virtually identical levels (17.4 Ϯ 0.5 g in females and 17.4 Ϯ 0.8 g in males). Similar to studies investigating other treatment factors and discussed previously (18), there were no significant interactions between treatment and the factors litter and sex.…”

Section: Methodssupporting

confidence: 91%

“…The program Statistica 5.5 (StatSoft, Tulsa, OK) was used for multifactorial analysis of variance (ANOVA) including factor repetition if required. In the analysis of the course of body mass development, the factors considered were treatment and age (repeated measurements), and in addition litter and sex, to take into account variabilities introduced by these parameters according to preceding investigations (18,38). Average data values were described by least square means (ϮSE) provided by ANOVA.…”

Section: Methodsmentioning

confidence: 99%

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MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

Schoelch

Hübschle

Schmidt

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Schoelch, Corinna, Thomas Hü bschle, Ingrid Schmidt, and Barbara Nuesslein-Hildesheim. MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure. Am J Physiol Endocrinol Metab 283: E604-E611, 2002. First published April 23, 2002 10.1152/ajpendo.00439.2001.-Suckling-age rats display endogenous circadian rhythmicity of metabolic rate (MR) with energy-saving, torpor-like decreases, which are sympathetically controlled and suppressed by leptin treatment. We investigated whether neonatal monosodium glutamate (MSG) treatment, known to cause arcuate nucleus damage and adult-age obesity, alters energy balance in the first two postnatal weeks. Continuously recorded MR and core temperatures (Tc) show that MSG treatment disinhibits the periodic, sympathetically controlled, energy-saving drops of Tc and MR. Increased energy expenditure thus explains reduced body fat at normal lean body mass found in MSGtreated pups artificially nourished identically to controls. In MSG-treated mother-reared pups, lean body mass is additionally reduced, suggesting that MSG also reduces suckling. Plasma leptin levels are similar in controls and MSG-treated pups but higher per unit of fat mass in the latter. We conclude that the postweaning development of MSG obesity and depressed thermogenesis are preceded by an early phase of increased energy expenditure with decreased fat deposition during suckling age and hypothesize cell damage in the arcuate nucleus to be involved in both. monosodium glutamate; juvenile rat; arcuate nucleus; obesity; leptin; torpor RODENTS TREATED POSTNATALLY with monosodium glutamate (MSG) develop into obese, stunted adults (4, 29, 37) and have been studied frequently as models for obesity. Postnatal MSG treatment produces central nervous (CNS) neurotoxic cell destruction, with the arcuate nucleus (ARC) as the most sensitive structure (35). With MSG doses sufficient to induce adult-age obesity but low enough to avoid extensive destruction such as retinal lesioning and tail automutilation (3,22,29), the CNS damage is seen in the ventromedial hypothalamus (VMH) and especially the ARC, two brain regions involved in the control of food intake. ARC damage is associated with impaired secretion of the releasing hormones for growth hormone (GHRH) and luteinizing hormone (LHRH) (2, 32), and the resulting changes in adenohypophysial growth hormone (GH) and gonadotropin secretion would explain retarded lean body mass growth and aberrations of gonadal development (19,36). Moreover, in the ARC, neuropeptide Y (NPY) production is almost completely, and proopiomelanocortin (POMC) production distinctly, reduced (1, 16). With these alterations of two peptide systems contributing importantly to the control of food intake and energy expenditure, mice (29, 37) and rats (22) are more or less hypophagic but ultimately become obese. MSG-induced damage of the ARC as the origin of these peptidergic pathways further implies impairment of the neuronal targets for circulating leptin as a hormone ...

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Section: Methodssupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

Schoelch

Hübschle

Schmidt

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…As in previous studies [16,30], when the data on body composition, body mass, FI, and MR of pups were evaluated, we took into account the considerable between-litter variability in growth [21,30,35] as well as the gender-related differences in these variables by considering a combined litter-gender effect as the second factor (besides treatment) in the two-way ANOVA statistics for each of the age groups. This was done by simply assigning different litter numbers to male and female littermates.…”

Section: Discussionmentioning

confidence: 99%

Developmental and food-access-dependent changes in effector systems activated by leptin

Eiden

Doering

Schmidt

2002

Pfl�gers Archiv European Journal of Physiology

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In small mammals leptin reduces fat stores not only by inhibiting food intake but also by disinhibiting metabolic cold defense. Presuming that postnatal age and feeding regime set the conditions for either mode of leptin action, we compared the caloric equivalents of changes in fat mass, metabolic rate (MR) and food intake (FI) induced by 10-day treatments with leptin, in rats treated from postnatal days 7, 15, 25 onward and in adult mice that were free-feeding or food restricted. Whereas MR changes are known to dominate from postnatal days 7-16, changes in MR explained only about 50% and 30% of the leptin-induced changes in fat mass between days 15-24 and days 25-34, respectively. In adult mice of similar body weights, leptin-induced reductions in fat mass under free-feeding conditions were due only to FI decreases but due only to MR increases under food-restricted conditions. Thus, the same leptin treatment induces the same percentage decrease in body fat content by driving the two effectors differently, depending on age and feeding conditions. Consequently, in assessing the effects of leptin under various physiological conditions, short-term measurements of FI or MR alone are not sufficient. Instead, determination of the resultant decreases in total body fat is required.

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“…The Zucker rat has been recognized as a superior model to investigate effects of obesity on chronic disease development, including cancer (Bray, 1977;de Assis et al, 2006;Hakkak et al, 2007), but its utility for investigations of mammary carcinogenesis is limited due to scant epithelial development in mature mammary glands of obese as compared with lean counterparts (Hu et al, 2002). Since it was reported that young heterozygous lean Zucker (+/fa) rats demonstrate a number of differences from wild type lean Zucker (+/+) rats, e.g., higher body weights, fat cell size, inguinal fat pad weights, pad-to-body weight ratios, serum cholesterol, adipose tissue lipoprotein lipase and glycerol-3-phosphate dehydrogenase, hepatic and adipose tissue 6-phosphogluconate dehydrogenase activities and serum leptin levels (1.6 and 0.9 ng/ml in +/fa and +/+, respectively, ) Heo et al, 2002;Phillips and Cleary, 1994;Truett et al, 1995;Zhang et al, 1997), we here investigated whether they might provide the basis for a leptin-related mammary carcinogenesis model. Two independent experiments were performed.…”

Section: Introductionmentioning

confidence: 99%

Female heterozygous (+/<i>fa</i>) Zucker rats as a novel leptin-related mammary carcinogenesis model

et al. 2012

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-The homozygous mutant fatty Zucker rat (fa/fa) is the prominent model for the research of obesity, one of the most well-known risk factor of postmenopausal mammary cancer. But the usage as a mammary gland carcinogenesis model is considered to be restricted due to the hypoplasia of mammary gland. In the present study, to find the validity of heterozygous mutant (+/fa) lean Zucker rats as a new leptin-related mammary carcinogenesis model, we examined whether the number of terminal end buds of mammary gland, the serum biochemistry, leptin concentration in serum and adipose tissue are changed in 7-week-old female +/+, +/fa and fa/fa rats, and whether these changes and leptin, TNF-α and VEGF mRNA expression in adipose tissue of +/+ and +/fa rats are influenced by 10% corn oil diet for 5 weeks. We confirmed that mild hyperleptinemia was more pronounced in 7-week-old +/fa as compared with wild type (+/+) and hypoplasia of mammary glands characterized by fewer numbers of terminal end buds in fa/fa was not observed in +/fa. With 10% corn oil diet, leptin mRNA expression in adipose tissue showed increasing tendency both in +/fa and +/+. Comparing with +/+, adipose tissue in +/fa treated with 10% corn oil diet was found to be significantly increased in the concentration of leptin protein and tended to be elevated expression of TNF-α mRNA. These results suggest that +/fa with 10% corn oil diet may be a useful model for investigation of the participation of leptin and TNF-α in mammary gland carcinogenesis.

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Codominant effects of the fatty (fa) gene during early development of obesity

Cited by 16 publications

References 11 publications

MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

MSG lesions decrease body mass of suckling-age rats by attenuating circadian decreases of energy expenditure

Developmental and food-access-dependent changes in effector systems activated by leptin

Female heterozygous (+/<i>fa</i>) Zucker rats as a novel leptin-related mammary carcinogenesis model

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