Differential effects of leptin on adiponectin expression with weight gain versus obesity
The relationship between obesity, leptin, adiponectin and the components of .. The primary goal of this study was to investigate the relationship between. Adiponectin and leptin: effects of dietary, metformin, and orlistat interventions. % of total. Diet component .. A 5% to 10% goal is, therefore, rec- ommended for weight women, and reported a correlation between lep- tin and BMI and waist. Adipocyte-derived hormones, leptin and adiponectin, are likely candidates The primary goal of these analyses was to determine any ethnic differences in models to examine the relation of leptin and adiponectin with CRP.
Additionally, the 15 min treatment to examine the leptin-dependent activation of cell signaling pathways and 6 hour treatment to examine the effects on mRNA transcripts were based on our previous experiments during which maximal responses would likely be observed. Statistical analysis Data were analyzed using JMP 9.
Changes in adiponectin and leptin during weight gain were compared using Pearson correlation. For the cross-sectional study, variables across the groups were compared using Wilcoxon rank sum test.
It was tested whether variance in the groups that were being statistically compared was similar. All in-vitro experiments were performed at least four times. Statistical significance and pairwise analysis were determined using Wilcoxon rank sum test. Results Effects of modest weight gain in healthy normal weight participants Increased calorie intake over a period of 8 weeks caused an average weight gain of 3.
The increase in total body weight resulted mainly from increased body fat mass 3. Among the variables measured, expected increases in insulin, and leptin were observed. Importantly, an increase in circulating adiponectin was observed with weight gain. On the other hand, the weight maintainer group did not show any changes in weight, total body fat mass, leptin or adiponectin during the 8 week follow-up.
There was also inter-individual variability in response to weight gain in the variables measured, including adiponectin and leptin. The changes in adiponectin ranged from 8.
Similarly, changes in leptin in the weight gain group ranged from The individual changes in these measures are depicted in Figure 1A.
CRP remained positively associated with leptin and inversely associated with adiponectin after adjustment for BMI and ethnicity Table 2 ; only the association with leptin reached statistical significance. In stratified models by BMI group, leptin remained statistically significant with similar magnitude of association with CRP, however, a statistically significant inverse association with adiponectin was only observed in overweight and obese women.
Association of leptin and adiponectin with CRP by ethnicitya. Discussion Using baseline data from a nutritional intervention study in premenopausal women, the authors found ethnic differences in levels of adipokines and inflammatory markers with variation by BMI.
Significantly lower leptin levels and consistently lower levels of the inflammatory markers CRP and IL-6 were observed in Asians than in Caucasians among overweight and obese, but not normal weight women. Because lower plasma adiponectin levels and higher leptin, CRP, and IL-6 levels are associated with metabolic disorders [ 162425 ], our findings suggest that the higher risk of chronic disease among Asians compared to Caucasians, particularly within the normal-weight range, may be in part due to lower adiponectin rather than leptin levels or proinflammatory marker levels.
Of interest, in overweight and obese women, Asians showed stronger associations for CRP with leptin and adiponectin compared to Caucasians. The findings support the hypothesis that leptin and adiponectin link adipose tissue with inflammation and suggest that adiponectin may play a role in the elevated risk for chronic disease despite lower BMI and leptin levels in Asian women. Consistent with findings from the present study, lower serum adiponectin levels independent of BMI have been observed in women of Chinese [ 18 ], Korean [ 19 ], and South Asian [ 1821 ] ancestry than in Caucasian women.
Low adiponectin levels are associated with abnormal glucose homeostasis, abnormal lipid metabolism, and insulin resistance in normal and in overweight or obese women [ 2627 ]; however, it is unclear whether low adiponectin levels mediate higher disease risk in Asians compared to Caucasians with comparable BMI [ 1821 ]. Because a clustering of increased metabolic, adipogenic, and proinflammatory factors are associated with lower adiponectin levels [ 28 ], complex multifactorial mechanisms of many contributing mediators may be involved rather than any single mechanism.
One hypothesis is that higher proportions of abdominal visceral relative to subcutaneous adiposity among Asians than Caucasians [ 45 ] may account for the observed lower levels of adiponectin in Asian women as serum adiponectin levels are determined predominantly by visceral rather than subcutaneous adipose tissue [ 1129 ].
The accumulation of visceral adiposity is associated with metabolic risk factors for diabetes and cardiovascular disease [ 30 ] and adiponectin may be an important mediator [ 3132 ].
The finding that leptin is a stronger predictor of CRP than adiponectin is consistent with other studies [ 3334 ]. Adipose tissue represents a common source for both leptin and these inflammatory cytokines, which are secreted by adipocytes [ 3637 ] and macrophages residing in adipose tissue [ 38 ]. In this and other studies in apparently healthy women [ 3940 ], leptin predicted CRP levels independent of BMI, suggesting that adipose tissue only partially mediates the leptin-CRP association, and alternative pathways unrelated to general adiposity may be involved.
Metabolic Syndrome | Adiponectin | Leptin | Orlistat | Metformin
For example, leptin may upregulate CRP levels by directly inducing IL-6 production [ 41 ] and by the leptin receptor, which has been shown to have intracellular signaling capabilities of ILtype cytokine receptors [ 42 ]. In this study, adiponectin was inversely associated with CRP in overweight and obese women only, whereas the adiponectin-CRP association was independent of BMI in previous studies among apparently healthy postmenopausal women [ 28 ] and women with type-2 diabetes [ 44 ].
However, adiponectin may have divergent prognostic implications depending on the population characteristics. Leptin and adiponectin were stronger predictors of CRP among Asian than Caucasian overweight and obese women, but not in overall BMI-adjusted models indicating that leptin and adiponectin link adipose tissue with inflammation and the underlying mechanisms may be heterogeneous across ethnic groups. A limitation of the study is the possibility of a Type I error due to assessing multiple correlations with small numbers of measured serum variables; therefore, our results are explorative and hypothesis-generating only.
Furthermore, the study included only a few women at the low and high extremes for BMI i.
Leptin, Adiponectin, and Obesity among Caucasian and Asian Women
As with any cross-sectional design, the directionality of associations remains unclear. Also, we did not have measures of abdominal fat distribution visceral versus subcutaneous or total body fat and were unable to assess whether the addition of measures for visceral adiposity attenuated ethnic-specific associations. It is possible that leptin, CRP, or IL-6 levels may be confounded by ethnic differences in inflammatory or autoimmune conditions [ 45 ]; however, this is unlikely given that the women in this study were apparently healthy and relatively young.
Additional outcome measures of interest that may have further elucidated the significance of lower adiponectin in Asian women with respect to metabolic markers include plasma glucose, insulin and lipid profiles, and visfatin, an adipocyte-derived protein predominantly found in visceral adipose tissue.
Mediators of Inflammation
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