Dynamics of Fat Mass in DUhTP Mice Selected for Running Performance - Fat Mobilization in a Walk.

Objective: Reduction of body fat can be achieved by dietary programs and/or aerobic exercise training. More convenient methods to rid the body of excess fat are needed. However, it is unclear whether it is possible to more easily lose body weight at all.

Lifelong obesity in a polygenic mouse model prevents age- and diet-induced glucose intolerance- obesity is no road to late-onset diabetes in mice.

Aims/hypothesis: Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance.

Methods: We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age- and high fat diet-dependent glucose tolerance.

High-fat diets rich in ω-3 or ω-6 polyunsaturated fatty acids have distinct effects on lipid profiles and lipid peroxidation in mice selected for either high body weight or leanness.

Objective: The aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of mice-high body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in ω-3 or ω-6 polyunsaturated fatty acids (PUFA).

Methods: The isocaloric HFDs were enriched with either ω-3 PUFA (27% fish oil, ω-3 HFD) or ω-6 PUFA (27% sunflower oil, ω-6 HFD), and the control group was fed standard chow (7.2% fat).

Metabolic adaptations in the liver of born long-distance running mice.

Purpose: Long-distance runners have increased needs of energy supply. To unravel genetically based mechanisms required for efficient energy supply, we have analyzed hepatic metabolism of mice characterized by the inborn capacity to perform as long-distance runners.

Methods: The mouse model had been established by phenotypic selection for high treadmill performance for 90 generations and was characterized by approximately 3.

Extrinsic and intrinsic regulation of DOR/TP53INP2 expression in mice: effects of dietary fat content, tissue type and sex in adipose and muscle tissues.

Background: DOR/TP53INP2 acts both at the chromosomal level as a nuclear co-factor e.g. for the thyroid hormone receptor and at the extrachromosomal level as an organizing factor of the autophagosome.

Phenotype selection reveals coevolution of muscle glycogen and protein and PTEN as a gate keeper for the accretion of muscle mass in adult female mice.

We have investigated molecular mechanisms for muscle mass accretion in a non-inbred mouse model (DU6P mice) characterized by extreme muscle mass. This extreme muscle mass was developed during 138 generations of phenotype selection for high protein content. Due to the repeated trait selection a complex setting of different mechanisms was expected to be enriched during the selection experiment.

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes.

Background: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.

Methods: The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.

High-protein diet in lactation leads to a sudden infant death-like syndrome in mice.

Background: It is well accepted that reduced foetal growth and development resulting from maternal malnutrition are associated with a number of chronic conditions in later life. On the other hand such generation-transcending effects of over-nutrition and of high-protein consumption in pregnancy and lactation, a proven fact in all developed societies, are widely unknown. Thus, we intended to describe the generation-transcending effects of a high-protein diet, covering most relevant topics of human life like embryonic mortality, infant death, and physical health in later life.

Increased fat mass, decreased myofiber size, and a shift to glycolytic muscle metabolism in adolescent male transgenic mice overexpressing IGFBP-2.

To elucidate the functional role of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) for in vivo skeletal muscle growth and function, skeletal muscle cellularity and metabolism, expression of signal molecules, and body growth and composition were studied in a transgenic mouse model overexpressing IGFBP-2. Postnatal growth rate of transgenic mice was reduced from day 21 of age by 6-8% compared with nontransgenic controls. At 10 wk of age body lean protein and moisture percentages were lower, whereas fat percentage was higher in IGFBP-2 transgenic mice.

Genetic control of lipids in the mouse cross DU6i x DBA/2.

An F(2) pedigree based on the mouse lines DU6i and DBA/2 with extremely different growth and obesity characteristics was generated to search for QTLs affecting serum concentrations of triglycerides (TG), total cholesterol (CHOL), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C). Compared with many other studies, we searched for spontaneous genetic variants contributing to high lipid levels under a standard breeding diet. Significant QTLs for CHOL were identified on chromosomes 4 and 6, and a female-specific locus on chromosome 3.

Two high-fertility mouse lines show differences in component fertility traits after long-term selection.

Unlabelled: Two selected high-fertility mouse lines, namely FL1 and FL2, and a non-selected control (Fzt:DU), all derived from the same genetic pool, were analysed as an animal model for polytocous species to elucidate the effects of long-term selection and to identify relevant component traits that may be responsible for fertility performance. The index trait used for breeding selection was largely increased by 104% and 142% in the FL1 and FL2 lines, respectively, resulting in an average litter size of 17.3 pups and 18.

Differentially expressed genes in adipose tissues of high body weight-selected (obese) and unselected (lean) mouse lines.

Recently, quantitative trait loci (QTLs) for body weight and obesity have been mapped in an intercross population between the high body weight-selected mouse line DU6i and the inbred line DBA/2. Most QTLs were highly significant, but had small effects only. Under the hypothesis that small-effect QTLs might result from changes in gene activity, our strategy to identify candidate genes for the observed effects was directed towards the identification of differentially expressed genes.

Chromosome-wise dissection of the genome of the extremely big mouse line DU6i.

The extreme high-body-weight-selected mouse line DU6i is a polygenic model for growth research, harboring many small-effect QTL. We dissected the genome of this line into 19 autosomes and the Y chromosome by the construction of a new panel of chromosome substitution strains (CSS). The DU6i chromosomes were transferred to a DBA/2 mice genetic background by marker-assisted recurrent backcrossing.

Relationships between quantitative and reproductive fitness traits in animals.

The relationships between quantitative and reproductive fitness traits in animals are of general biological importance for the development of population genetic models and our understanding of evolution, and of great direct economical importance in the breeding of farm animals. Two well investigated quantitative traits--body weight (BW) and litter size (LS)--were chosen as the focus of our review. The genetic relationships between them are reviewed in fishes and several mammalian species.

Effects of the compact mutant myostatin allele Mstn (Cmpt-dl1Abc) introgressed into a high growth mouse line on skeletal muscle cellularity.

The murine myostatin mutation Mstn(Cmpt-dl1Abc) (Compact; C) was introduced into an inbred mouse line with extreme growth (DUHi) by marker-assisted introgression. To study the allelic effects on muscle fibre hyperplasia and hypertrophy, myonuclear proliferation, protein accretion, capillary density, and muscle fibre metabolism, samples from M. rectus femoris (RF) and M.

Marker-assisted introgression of the Compact mutant myostatin allele MstnCmpt-dl1Abc into a mouse line with extreme growth effects on body composition and muscularity.

Myostatin is a negative regulator of muscle growth and mutations in its gene lead to muscular hypertrophy and reduced fat. In cattle, this is seen in 'double muscled' breeds. We have used marker-assisted introgression to introduce a murine myostatin mutation, MstnCmpt-dl1Abc [Compact (C)], into an inbred line of mice (DUHi) that had been selected on body weight and had exceptional growth.

QTLs for pre- and postweaning body weight and body composition in selected mice.

In an intercross between the high-body-weight-selected mouse line NMRI8 and the inbred line DBA/2, we analyzed genetic effects on growth during the suckling period and after weaning during the juvenile phase of development. QTL mapping results indicated that a switch of gene activation might occur at the age of three weeks when animals are weaned. We found QTLs for body weight with major effects at the age of two and three weeks when animals are fed by their mothers, and QTLs with highest effects after weaning when animals have to live on their own under ad libitum access to food.

Long-term growth selection of mice changes the intrinsic susceptibility of myogenic cells to apoptosis.

Myogenic cells were derived from mice long-term selected over 70 generations for high 6-weeks body weight (DU-6) and from unselected control mice (DU-Ks). The cells were grown in medium with 10% foetal bovine serum (FBS) for 8 days or transferred to low serum conditions (1% FBS) at days 4 and 6 of cultivation, respectively, and maintained for two further days. In both cell lines, serum reduction induced decreases in DNA and protein contents, and in DNA synthesis rate.

Carbon and nitrogen content based estimation of the fat content of animal carcasses in various species.

The objective of this study was to explore whether the C and N content can be used to estimate the fat content of animal carcasses. Considering the mean C and N contents of body fat and body protein, the fat content (EE) [%] can be predicted from C and N values [%] according to the generally valid equation EE = 1.3038 x C - 4.

Growth selection in mice reveals conserved and redundant expression patterns of the insulin-like growth factor system.

Transgenic and knockout models have been used successfully in order to attribute specific functions to distinct growth factors. However, it is not clear which from the different IGF-components are actually altered when growth is affected. Furthermore it is not clear if unique or redundant patterns of IGF-component expression are present under conditions of elevated or reduced growth.

Susceptibility to apoptosis in different murine muscle cell lines.

Objective of the study was to investigate growth characteristics and susceptibility to apoptosis in different murine muscle cell lines (selected for high body weight, DU-6; randomly mated control, DU-Ks; immortalized myoblast cell line, C2C12). Apoptosis was induced by serum deprivation. At days 4, 5, and 6 of cultivation, protein, DNA and the frequency of apoptotic cells were determined.