Diet-induced Obese Mice Are Leptin Insufficient After Weight Reduction

Obesity Research Center, Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio, USA.
Obesity (Impact Factor: 3.73). 05/2009; 17(9):1702-9. DOI: 10.1038/oby.2009.106
Source: PubMed


Behavioral therapies aimed at reducing excess body fat result in limited fat loss after dieting. To understand the causes for maintenance of adiposity, high-fat (HF) diet-induced obese (DIO) mice were switched to a low-fat chow diet, and the effects of chow on histological and molecular alterations of adipose tissue and metabolic parameters were examined. DIO mice reduced and stabilized their body weights after being switched to chow (HF-chow), but retained a greater amount of adiposity than chow-fed mice. Reduction in adipocyte volume, not number, caused a decrease in fat mass. HF-chow mice showed normalized circulating insulin and leptin levels, improved glucose tolerance, and reduced inflammatory status in white adipose tissue (WAT). Circulating leptin levels corrected for fat mass were lower in HF-chow mice. Leptin administration was used to test whether reduced leptin level of HF-chow mice inhibited further fat loss. Leptin treatment led to an additional reduction in adiposity. Finally, HF-HF mice had lower mRNA levels of beta(3) adrenergic receptor (beta(3)-AR) in epididymal WAT (EWAT) compared to chow-fed mice, and diet change led to an increase in the WAT beta(3)-AR mRNA levels that were similar to the levels of chow-fed mice, suggesting an elevation in sympathetic activation of WAT during diet switch relative to HF-HF mice leading to the reduced leptin level and proinflammatory cytokine content. In summary, HF-chow mice were resistant to further fat loss due to leptin insufficiency. Diet alteration from HF to low fat improved metabolic state of DIO mice, although their adiposity was defended at a higher level.

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Available from: Haifei Shi, Oct 03, 2014
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    • "It has also been shown that weight cycling under such conditions leads to substantial modification of blood lipids, glucose and insulin homeostasis, adipokine levels, and proinflammatory cytokines (Barbosa-da-Silva et al., 2012), and a structural remodelling of the liver (Barbosa-da-Silva et al., 2013), changes which were not reversed when mice lost body weight during the switch to chow feeding (Barbosa-da-Silva et al., 2012, 2013). In addition, the increase in adiposity resulting from high fat diet feeding cannot easily be reversed by reducing body weight when switching back to chow feeding; mice retained the increased number of adipocytes that were accumulated during high fat diet feeding, although adipocyte volumes were reduced (Shi et al., 2009). A decreased activity level had been suggested as a responsible mechanism for weight gain during weight cycling (Barbosa-da-Silva et al., 2012). "
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    • "These compensatory changes in EE oppose the maintenance of reduced BW and likely cause the recidivism to obesity. As shown in multiple studies, these processes are mediated by a coordinated endocrine response involving leptin, ghrelin, thyroxin, and other hormones modifying food intake, EE and factors that influence BW-regulation [3]–[5]. In addition, there is a growing body of evidence from human and rodent studies for a crucial role of estrogens in the regulation of BW-loss, -maintenance, and -regain. "
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    PLoS ONE 05/2012; 7(5):e37794. DOI:10.1371/journal.pone.0037794 · 3.23 Impact Factor
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    • "Our results suggest that PI3K signalling in VMH neurons may play an important role in resisting diet-induced obesity. However, we did not formally examine if the obese phenotypes seen in HFD-fed p110α lox/lox /SF1-Cre mice can be blunted by switching from HFD back to regular chow, which is characteristically seen in diet-induced obesity (Enriori et al., 2007; Shi et al., 2009). "
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