Influence of diet on the modeling of adipose tissue triglycerides during growth

Abstract

We have studied the accretion of lipids in growing mice. We measured the rates of synthesis and degradation of triglycerides in epididymal fat pads of mice maintained for 44 days on a low-fat, high-carbohydrate diet (I) or a high-fat, lowcarbohydrate diet (II).2 H2O was added to the drinking water for 14 days. Rates of incorporation/washout of 2 H to/from C1 of triglyceride-glycerol showed that triglyceride synthesis was greater than triglyceride degradation (net triglyceride balance was ϳ2.5 times greater in II than in I). The data also show that the contribution of de novo lipogenesis to triglyceride-bound palmitate was ϳ3 times greater in I than in II. This was consistent with a greater relative intake of carbohydrate in I vs. II. The rates of incorporation and washout of newly synthesized ( 2 H-labeled) palmitate into and from triglycerides were also measured. Those data suggested a remodeling of triglyceridebound fatty acids. On measuring the profile of triglyceridebound fatty acids, we observed a decrease in the relative abundance of triglyceride-bound palmitate and stearate and an increase in triglyceride-bound oleate and linoleate. This was observed in I and II. In summary, diet substantially affects the deposition and modeling of triglycerides in adipose tissue during growth. 2 H2O can be used to examine the mechanisms responsible for the accumulation of triglycerides, e.g., factors that affect 1) triglyceride synthesis and degradation and 2) the source of fatty acids that are used in esterification. deuterium; stable isotopes; lipid metabolism; pediatric obesity; insulin resistance THERE IS AN ALARMING INCREASE in the number of reported cases of pediatric obesity (26, 32). Like obese adults, obese children present with metabolic abnormalities (e.g., impaired glucose tolerance, dyslipidemia) that are associated with an increased risk of developing a chronic disease (e.g., diabetes, cardiovascular disease) (8,9,21,24,32). A special concern regarding obese children is that many will remain obese as adults, which further increases the likelihood of developing a chronic disease. Presumably, the development of effective treatments for pediatric obesity will benefit from knowledge of how specific biochemical reactions drive lipid accumulation during growth.We hypothesized that, during growth, the nature of one's caloric intake will affect the rate of, and the mechanism of, fat accumulation. For example, as the ratio of dietary fat to carbohydrate increases, the rate of triglyceride accretion will increase. Also, the relative amount of carbohydrate in the diet will affect the relative contribution of de novo lipogenesis to the pool of triglyceride-bound fatty acids. We developed the use of 2 H 2 O to measure the rates of the reactions involved in triglyceride accumulation (e.g., triglyceride synthesis and triglyceride degradation and the contribution of de novo lipogenesis to the pool of triglyceride-bound fatty acids). This approach also allows us to determine the rate of remodeling of fatty acids that are bo...

Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

“…Furthermore these results implicate increased rates of adipocyte lipolysis, and not an increase in insulin stimulation of hepatic lipogenesis, as the major culprit in the pathogenesis of NAFLD. These findings are consistent with studies demonstrating increased TG synthesis from dietary fatty acids in fat-fed mice (31,32). Our hypothesis would also explain the apparently paradoxical finding of unchanged or decreased hepatic fat content in T2D patients treated with insulin (33)(34)(35).…”

Triglyceride Synthesis in Epididymal Adipose Tissue

“…growth) and that de novo lipogenesis can make a major contribution to the pool of fatty acids used in the generation of new triglycerides (e.g. Ͼ90% of the newly deposited palmitate can be derived from de novo lipogenesis) (6). In addition, we observed a vigorous remodeling of the fatty acid distribution profile (6).…”

“…Ͼ90% of the newly deposited palmitate can be derived from de novo lipogenesis) (6). In addition, we observed a vigorous remodeling of the fatty acid distribution profile (6). Using 2 H 2 O, Hellerstein and colleagues (7,8) have demonstrated that rates of triglyceride turnover in adipose tissue are depot-specific and sensitive to pharmacological therapy.…”

“…In all cases, to ensure the precision of the injection, mice were sedated by a brief exposure (ϳ15 s) to isoflurane (Baxter Pharmaceuticals, Deerfield, IL); mice regained consciousness within a minute with no apparent adverse side effects. After injection, mice were returned to their cages (n ϭ four mice per cage) and maintained on 5% 2 H-labeled drinking water for the remainder of the study; this design maintained a steady-state 2 H labeling of body water at ϳ2.75% (6). Mice in each group were fed the respective diets ad libitum, and daily food consumption was measured.…”

“…2 H Labeling of Triglyceride-bound Glycerol-Total glycerides were extracted from frozen epididymal fat pads by first hydrolyzing both fat pads in 1 N KOH ethanol at 70°C (6). After 3 h, the hydrolysate was evaporated to dryness, and the dry residue was redissolved in 3 ml of H 2 O and acidified to ϳpH 1.0 by adding 6 N HCl.…”