Body Fat In Mice Research Articles

Mutation of a novel gene results in abnormal development of spermatid flagella, loss of intermale aggression and reduced body fat in mice.

ROSA22 male mice are sterile due to a recessive gene-trap mutation that affects development of the spermatid flagellum. The defect involves the flagellar axoneme, which becomes unstable around the time of its assembly. Despite a subsequent complete failure in flagellar assembly, development of the spermatid head appears normal and the spermatid head is released at the correct stage in spermatogenesis. The mutation is pleiotropic. Although ROSA22 homozygote males have normal levels of circulating testosterone and display normal mating behavior, they do not exhibit intermale aggressive behavior and have reduced body fat. The mutated gene (Gtrgeo22) maps to mouse chromosome 10 and is closely flanked by two known genes, Madcam1 and Cdc34. Ribonuclease protection analysis indicates that expression of the flanking genes is unaffected by the mutation. Gtrgeo22 is expressed at low levels in epithelial cells in several tissues, as well as in testis and brain. Analysis of the peptide coding sequence suggests that Gtrgeo22 encodes a novel transmembrane protein, which contains dileucine and tyrosine-based motifs involved in intracellular sorting of transmembrane proteins. Analysis of the Gtrgeo22 gene product should provide novel insight into the molecular basis for intermale aggression and sperm flagellar development.

The Decrease in Body Fat in Mice Fed Conjugated Linoleic Acid Is Due to Increases in Energy Expenditure and Energy Loss in the Excreta

We carried out energy balance studies in four groups of young, growing, 5-wk-old Balb-C mice (n = 12/group) that were either food restricted or nonrestricted and fed high fat diets (38 energy%) with or without 0.93 g/100 g conjugated linoleic acid (CLA) for 39 d. The energy in carcasses, excreta and food was measured in a bomb calorimeter. CLA lowered the percentage of the energy intake that was stored in the body from 1.9 +/- 0.8 to -2.3 +/- 0.7% (mean +/- SD, P < 0.05) in the nonrestricted mice and from 1.4 +/- 1.3 to -2.9 +/- 0.7% (P < 0.05) in the restricted mice. Thus, the CLA-treated mice had a net loss of body energy. The percentage of the energy intake eliminated in the excreta increased from 7.6 +/- 0.9% in controls to 8.7 +/- 1.0% (P < 0.05) in the CLA-treated mice that were nonrestricted and from 7.3 +/- 0.8 to 8.4 +/- 0.6 (P < 0.05) in the restricted mice. The amount of energy ingested minus the amount retained in carcasses and excreta equals the energy expenditure. The percentage of the energy intake that was expended as heat increased from 90.5 +/- 1.2 in controls to 93.6 +/- 1.5% (P < 0.05) in the CLA-treated nonrestricted mice and from 91.3 +/- 1.5 to 94.5 +/- 1.0% (P < 0.05) in the restricted mice. The lower energy storage in the CLA-fed mice was accounted for by an increase in the energy expenditure (74%) and by an increase in energy lost in the excreta (26%). Feeding CLA also increased liver weight, which may warrant further studies on the safety of CLA.

The trans-10,cis-12 Isomer of Conjugated Linoleic Acid Downregulates Stearoyl-CoA Desaturase 1 Gene Expression in 3T3-L1 Adipocytes

Conjugated linoleic acids (CLA) are a group of positional and geometric conjugated dienoic isomers of linoleic acid. The objective of this study was to determine the effects of the cis-9,trans-11 and trans-10,cis-12 isomers of conjugated linoleic acid on lipid composition and gene expression during the differentiation of mouse 3T3-L1 preadipocytes. Treatment of differentiating 3T3-L1 preadipocytes with trans-10,cis-12 conjugated linoleic acid (CLA) resulted in a dose-dependent decrease in the expression of the stearoyl-CoA desaturase 1 gene (SCD1). The expression of other adipocyte genes such as adipose P2 (aP2), fatty acid synthase (FAS), SCD2 and the key adipogenic transcription factors, peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT enhancer binding protein alpha (C/EBPalpha), remained elevated. Cells treated with trans-10,cis-12 CLA exhibited smaller lipid droplets, with reduced levels of the major monounsaturated fatty acids, palmitoleate and oleate. By contrast, the cis-9,trans-11 isomer did not alter adipocyte gene expression. Repression of the stearoyl-CoA desaturase gene expression in adipocytes by the trans-10,cis-12 isomer may contribute to the mechanisms by which CLA reduces body fat in mice.

Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA.

Glucocorticoid stimulation of appetite and leptin expression conflicts with leptin inhibition of food intake and suggests that glucocorticoids reduce sensitivity to leptin. To determine if glucocorticoids impair feeding and metabolic responses to leptin, we measured leptin-induced changes in food intake, body weight, hormones, carcass fat, and hypothalamic neuropeptide Y (NPY) mRNA in adrenalectomized mice with and without corticosterone replacement. Leptin infusion (0.5 microgram/h) significantly decreased food intake and body weight in adrenalectomized mice. Corticosterone replacement approximating normal 24-h mean levels restored food intake but did not permit weight gain equivalent to PBS-infused controls. Corticosterone levels comparable to stress-induced production completely reversed leptin-induced reductions in weight gain and body fat, despite significant attenuation by leptin of corticosterone-induced increases in plasma insulin levels. Glucocorticoid replacement increased food intake without reversing leptin inhibition of hypothalamic NPY mRNA levels. We conclude that glucocorticoid levels within the physiological range can interfere with leptin action and that glucocorticoid effects are at least partly independent of NPY.

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.

Body fat of mice and men: A class exercise in theory or practice

An adaptation of some methods used in obesity research is presented as a teaching example to illustrate the use of 'animal models' in medical research. From sixth-form level upwards, it serves as a theoretical exercise in the analysis and interpretation of methods and data. For undergraduates it is also suitable as a laboratory exercise in dissection and measurement techniques. Four simple means of altering fat levels in laboratory mice are described, contrasting invasive injection techniques with non-invasive dietary and behavioural means. Several measures of body fatness can be evaluated, using either the experimental mice or, more simply, untreated mice from outbred stocks. Guidelines are given for practicals in which objective and subjective measures of fatness in human subjects can be collected. Sample data for mice are given that, alone or together with class-collected data, allow graphical and statistical analysis. Throughout, the exercise lends itself to discussion of the assumptions both of the methods used on mice and men, and of the relation of such investigations to the problems of overweight in man. Obesity has many manifestations: the study of a variety of ‘animal models’ is one approach in the search for relevant physiological knowledge.

Studies on the Biological Fate of Kelthane. I. Distribution and Excretion of &lt;SUP&gt;3&lt;/SUP&gt;H-Kelthane in the Mice

Distribution and excretion of 3H-1, 1-bis (4-chlorophenyl) 2, 2, 2-trichloroethanol (3H-kelthane) after oral dosaze were studied in mice. In the distribution study of 3H-kelthane, its radioactivity was detected in various tissues, indicating extensive uptake of this compound. The radioactivity distributed in each organ in mice reached a maximum after 24-48 hr and rapidly decreased thereafter with the exception of body fat. In particular, high level of radioactivity and its prolonged retention were observed in the body fat in mice. Approximately 60 % of the administered radioactivity was excreted in the urine (20 %) and feces (40 %) of mice within 96 hr, implying that fecal excretion is the major elimination route in the oral administration of kelthane.