| [Objective] To observe dynamic changes in body composition in adult catch-up growth (CUGA) rat model and explore the relationship between body composition and system insulin sensitivity in CUGA.[Methods] After1week of adaptive feeding, seven-week-old male Sprague-Dawley rats were divided into10groups at random. Rats in five of these groups were normal chow (NC) groups, which were fed normal chow ad libitum for4、5、6、8、12weeks, respectively. In contrast, rats in another5groups were catch-up growth with normal chow (RN) groups, which were provided with caloric restriction for4weeks and then respectively refed on0、1、2、4、8weeks. Body weights and energy intake were measured everyday. Body composition was assessed in vivo using dual-energy X-ray absorptiometry. And hyperinsulinemic-euglycemic clamp were performed to evaluate systemic insulin sensitivity.[Results]1. Compared with the corresponding NC groups, weekly energy intake was decreased in RN groups throughout the experiment.2. During calorie restriction, body-weight gain was significantly inhibited in rats of RN group as compared with corresponding NC group (P<0.05). After refeeding, body weight was increased rapidly in RN groups, while it was still lower in RN group than NC group on week8of refeeding (P<0.05).3. After4-week calorie restriction, percentage of body fat mass, percentage of abdominal fat mass and abdominal fat to body fat ratio were lower in RN group than NC group(P<0.05). After refeeding, percentage of body fat mass, percentage of abdominal fat mass and the ratio of abdominal fat to body fat in RN group were all increased with the time. On week2of refeeding, indicators above-mentioned in RN group were found to be significantly higher than in NC group (P<0.05). However, percentage of lean body mass showed an opposite trends to percentage of body fat mass in RN group and no significant difference in percentage of lean body mass was found between NC group and RN group throughout the experiment (P>0.05).4. In RN group, GIR60-120was positively correlated with the percentage of body fat mass, the percentage of abdominal fat mass and the ratio of abdominal fat to body fat (P=0.000), whereas there was no linear relationship between GIR60-120and the percentage of lean body mass(P=0.135). Among these factors, the ratio of abdominal fat to body fat exhibited more significant relationships with GIR60-120than percentage of body fat mass and percentage of abdominal fat mass.[Conclusion] The essence of CUGA is a progress that is characterized by a disproportionately higher rate of body fat than lean tissue gain and a redistribution of body fat. This preferential catch-up fat, especially the redistribution of body fat, may be a critical determinant for system insulin sensitivity in CUGA. [Objective] Catch-up growth in adult (CUGA), a trigger for later insulin resistant (IR)-associated diseases, is characterized by visceral fat accumulation, lipid overflow and insulin resistance. We aimed to investigate the determinant of visceral fat accumulation, lipid overflow and insulin resistance during CUGA as well as the interaction among them.[Methods] Seven-week-old male Sprague-Dawley rats were randomly divided into normal chow (NC) and catch-up growth with normal chow (RN) groups. Rats in NC groups were offered normal chow ad libitum for4、5、6、8、12weeks respectively, which were age-matched controls for RN groups. Rats in RN groups were put on caloric restriction for4weeks initially, and then refed with0、1、2、4、8weeks, respectively. In this study, general physiological and biochemical parameters, body compositions, average glucose infusion rate6o-120(GIR60-120) in hyperinsulinemic-euglycemic clamp as well as ectopic triglyceride contents were evaluated at the end of experiment. Moreover, morphology of perirenal adipocyte,2-deoxy-D-glucose (2-DG) and the expression of lipogenic genes, lipolytic genes and lipid storage-related genes were also detected.[Results]1. Change of metabolic parameters in rats:After4-week caloric restriction, percentage of abdominal fat mass was lower in RN group than NC group (P<0.05), and it was rapidly increased with the time after refeeding. On week2of refeeding, percentage of abdominal fat mass in RN group was found to be significantly higher than in NC group (P<0.05). No significant difference in serum non-esterified fatty acids (NEFA), serum fasting insulin, intramuscular and intrahepatic triglyceride contents as well as GIR60-120was found between NC group and RN group at the end of caloric restriction (P>0.05). However, after refeeding, serum NEFA, serum fasting insulin, and ectopic triglyceride contents in RN group were all gradually increased and the GIR60-120correspondingly reduced.2. Change of lipogenic parameters in rats:Compared with NC groups, expressions of peroxisome proliferator-activated receptor y (PPARy) and lipoprotein lipase (LPL) in perirenal adipose tissue (PAT) of RN groups were significantly up-regulated before and after refeeding (P<0.05). There was a slight increase in2-DG uptake and fatty acid synthesis activity in PAT in RN group relative to NC group after caloric restriction(P>0.05), and it was significantly elevated in RN groups after refeeding as compared to their controls (P<0.05).3. Change of lipid storage-related parameters in rats:By the end of4-week caloric restriction, gene expression of fat specific protein27(FSP27) were dramatically lower in RN group than NC group (P<0.05). By contrast, refeeding can partially moderated this trend. The lowered FSP27expression in RN group sustained till2-week of refeeding. On week4and8refeeding, FSP27expression had markedly elevated in RN groups relative to controls (P<0.05). Notably, there was a consistent decrease in the expression of perilipinl during caloric restriction and re-feeding (P<0.05). The HE staining disclosed that caloric restriction resulted in an obvious decrease in perirenal adipocyte size (P<0.05), and following re-feeding, the perirenal adipocyte increased but did not exceed the level of controls even eight weeks after the catch-up growth (P>0.05).4. FSP27gene expression consistently lagged far behind PPARy gene expression during CUGA as compared with the change in gene expression of PPARy in RN groups.5. Change of lipolytic parameters in rats:ATGL mRNA expression was significantly enhanced in RN group in comparison with NC group as a result of4-week caloric restriction (P<0.05), and this trend was more evident in RN groups than their controls. A similar expression profile of CGI-58mRNA was observed.[Conclusion] The is the first study that suggests the persistent caloric restriction-induced imbalance of lipogenesis/fat storage capacity might be mainly responsible for CUGA-associated metabolic disorders. [Objective] To observe the changes in visceral adipocyte apoptosis, visceral adipose tissue inflammation and systemic insulin sensitivity in adult catch-up growth(CUGA) rats and explore the potential mechanism for the development of insulin resistance in CUGA.[Methods] Seven-week-old male Sprague-Dawley rats were acclimatized for1week and then randomly assigned to either normal chow (NC) groups, fed ad libitum for4、6、8、12weeks, or catch-up growth by normal chow (RN) groups, provided4-week calorie restriction and then re-fed with normal chow for0、2、4、8weeks. At each experimental time-point, body composition was measured by dual-energy X-ray absorptiometry. Systemic insulin sensitivity was evaluated using hyperinsulinemic-euglycemic clamp. And the samples of perirenal adipose tissue directly for apoptosis cell were examined by transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, we also performed western blot to analyze the protein level of apoptosis-related gene, and carried out RT-PCR to assess the expression of inflammation markers in perirenal adipose tissue.[Results]1. At the end of4-week caloric restriction, percentage of abdominal fat mass was obviously lower in RN group than in NC group (P<0.05), and it was rapidly increased with the time after refeeding. On week2,4, and8of refeeding, percentage of abdominal fat mass in RN groups was found to be significantly higher than in NC group (P<0.05).2. After4-week caloric restriction, there was a tendency for insulin sensitivity determined by GIR60-120in hyperinsulinemic-euglycemic clamp to be higher in RN group, but it did not reach a statistically significant difference as compared with NC group (P>0.05). After refeeding, GIR60-12o decreased over time in RN groups. On week4and8of refeeding, it was markedly lower in RN group than NC group (P<0.05).3. There was no obvious difference in the quantification of TUNEL-positive adipocytes between RN and NC group by the end of4-weeks (P>0.05). In sharp contrast, the quantification of TUNEL-positive adipocytes after refeeding showed an evidently increase in the ratio of apoptotic cells in RN groups as compared to their corresponding controls.4weeks after refeeding, TUNEL-positive adipocyte was obviously higher in RN group than NC group, which increased even further after8-week of refeeding (P<0.05). A similar expression profile of apoptosis related-genes in RN groups was observed before and after refeeding.4. Gene expression of inflammation markers such as F4/80、MCP-1、TNFα'IL-6was significantly decreased as a result of4-week caloric restriction (P<0.05), this trend can be reversed by refeeding. On week4and8of refeeding, expression of these markers was markedly elevated in RN group as compared with NC group (P<0.05).5. In RN group, the ratio of TUNEL-positive adipocyte was positively correlated with the percentage of abdominal fat mass and the expression of F4/80mRNA, a macrophage-specific markers, but negatively correlated with GIR60-120in hyperinsulinemic-euglycemic clamp(P=0.000).[Conclusion] Visceral adipocyte apoptosis may be an important mechanism for system insulin resistance in CUGA. This might be ascribed to the chronic inflammation in visceral adipose tissue triggered by adipocyte apoptosis. |
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