Lipids, Jul 2009 by Tallman, Diana L, Noto, Amy D, Taylor, Carla G
Sir,
C57BL/6J mice are the background strain for multiple models of obesity and diabetes that have genes homologous to those identified in human obesity [1,2]. C57BL/6J mice are also models of gene-environment induced obesity because they are more susceptible to an environment permissive to obesity and several publications show that high fat (HF) feeding (~ 40-70% of kcal) induces obesity, insulin resistance, hyperglycemia and leptin resistance [3-9]. We have used this model of high fat feeding to examine interactions of obesity and zinc status but showed neither level of dietary fat nor zinc had an effect on body weight, body mass index, glycemia, insulinemia or leptinemia in C57BL/6J mice [10]. This led to an opportunity to examine whether the inconsistency in development of diet induced obesity (DIO) is related to dietary fat level, or the metabolic derangements associated with greater weight gain. Thus, mice from the original data set [10] were stratified into low body weight (LBW) and high body weight (HBW) groups to determine relationships with metabolic parameters associated with obesity including variations in adipose tissue fatty acid composition and zinc status.
The LBW and HBW groups comprised mice fed both low fat (LF) and HF diets, and similar numbers of zinc deficient, control and supplemented mice (Fig. 1). The HBW group displayed greater fasting serum glucose and leptin concentrations (9.8 0.5 vs. 8.2 0.6 mmol/L and 42.6 5.9 vs. 20.3 4.4 ng/ml, respectively; P
Our results also demonstrate that adipose PL fatty acid composition was affected by diet and obesity (Table 1), whereas adipose TAG fatty acid composition generally resembled the dietary fatty acid content. The HBW mice had more C16:0 (15.3 0.4 vs. 14.3 0.4%), C18:3n-3 (0.35 0.07 vs. 0.24 0.04%) and C22:5n-3 (0.52 0.02 vs. 0.46 0.02%), less C22:6n-3 (3.94 0.22 vs. 4.49 0.25%), and a greater n-6:n-3 ratio (5.88 0.24 vs. 5.15 0.23) in adipose PL compared to LBW mice. There was an interaction of diet fat and body weight such that the HBW-LF mice had more C18:3n-3 and less C20:5n-3 in adipose PL than the LBW-LF mice, suggesting reduced conversion of ALA to EPA in the HBW-LF mice (Table 1). These findings may be due to differences in delta 6 and delta 5 desaturation, /J-oxidation or incorporation into membrane PL [18, 19], but this study is limited by the fact that these factors were not examined. Interestingly, both desaturase enzymes are regulated by SREBP-1 and PPARa in mice [20], targeted genes in the pathology of obesity. Furthermore, people with diabetes have defects of delta 6 and delta 5 desaturases [21].
Insulin stimulates delta 6 desaturase and zinc is one cofactor, thus, it is also of interest that we have shown a reduced zinc concentration in adipose, pancreatic and liver tissue (Fig. 2a) in conjunction with a lower n-3 fatty acid status in adipose tissue PL in the HBW mice, independent of dietary fat (Table 1). However, when total zinc content was calculated in the same tissues, the effect was lost (Fig