![]() After weaning (35 d), 60 Lean and 60 Fat rabbits/room were housed by two in wire-mesh cages and fed ad libitum with commercial pellets. From birth to slaughter (13 weeks of age), the rabbits were housed in two rooms where the temperature was controlled with air conditioners: in the control room the average ambient temperature was 20 ☌ and in the high temperature room it was 28 ☌. The two genetic lines (Lean and Fat) were selected based on the total body fat content estimated by computer tomography during five generations. The study aimed at evaluating the effect of different ambient temperatures on the live performance and carcass traits of growing rabbits divergently selected for total body fat content. Rabbits are particularly sensitive to heat stress which can affect productive performance, with rabbit breed/line possibly playing a role on the response to this condition. Selection for lower total body fat content could be useful for terminal male lines, while the selection for higher total body fat content could be an advantage for rabbit does in providing fat (energy) reserves. The divergent selection for total body fat content showed to be effective for both lean and fat lines. On the contrary, rabbits of the fat line had the highest carcass adiposity (p < 0.001). Furthermore, the carcass of the lean rabbits had the highest proportion of fore (p < 0.020) and hind (p < 0.006) parts. The lean line showed a better feed conversion ratio (p < 0.001) than the fat line. Growth performance, dressing out percentage and carcass adiposity were measured. At generation four, 60 rabbits/line were housed in wire-mesh cages and fed with commercial pellet ad libitum from weaning (5 w of age) to slaughtering (11 w of age). The rabbits with the lowest fat index belonged to the lean line and those of the highest values belonged to the fat line. The fat index was determined at 10 weeks of age by computed tomography and lasted for four consecutive generations. The aim of this experiment was to study the effect of divergently selected rabbits for total body fat content (fat index) on growth performance and carcass traits. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. ![]() Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. Tst-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. Energy budget analysis indicated that the major line differences were in the level of energy expended on physical activity, and these differences were preserved following introgression, suggesting that multiple pathways regulate fatness, which may be independently responsive to intervention. ![]() Introgression of leptin production and receptor deficiencies had separate effects from long-term selection, indicating that the genes responsible for the line divergence must act independently of the leptin regulatory system. Concentrations of circulating leptin were relatively independent of the original lines but heavily dependent on the introgressed genotype. Line differences were, however, mostly maintained after introgression. The fat amount increased significantly in homozygotes for Lep(ob) or Lepr(db) in both lines, for example, in F and L males from 8.5 to 18.8 and 17.2 g (P<0.001) and from 1.25 to 18.0 and 12.7 g (P<0.001), respectively. To elucidate the importance of the leptin regulatory feedback loop in the genetic changes produced by this selection, Lep(ob) and Lepr(db) mutations causing leptin production and leptin receptor deficiency, respectively, were introgressed individually into both lines by repeated backcrossing. Divergent selection in mice on fatness over 60 generations produced a fat (F) and a lean (L) line, having about 22% and 4% body fat, respectively.
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