Mild Calorie Restriction Induces Fat Accumulation in Female C57BL/6J Mice

Li, Xingsheng; Cope, Mark B.; Johnson, Maria S.; Smith, Daniel L.; Nagy, Tim R.

doi:10.1038/oby.2009.312

Cited by 54 publications

(71 citation statements)

References 40 publications

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“…These changes in feeding behavior are consistent with food anticipatory activity (FAA) observed previously in rodents ( Fig. 3 A and B) (28)(29)(30)(31). Ift88 Δ/Δ mutant mice undergoing calorie restriction ate a majority of their daily food allowance within 3 h of access to food (Fig.…”

Section: Resultssupporting

confidence: 72%

Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice

Berbari¹,

Pasek²,

Malarkey³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Although primary cilia are well established as important sensory and signaling structures, their function in most tissues remains unknown. Obesity is a feature associated with some syndromes of cilia dysfunction, such as Bardet-Biedl syndrome (BBS) and Alström syndrome, as well as in several cilia mutant mouse models. Recent data indicate that obesity in BBS mutant mice is due to defects in leptin receptor trafficking and leptin resistance. Furthermore, induction of cilia loss in leptin-responsive proopiomelanocortin neurons results in obesity, implicating cilia on hypothalamic neurons in regulating feeding behavior. Here, we directly test the importance of the cilium as a mediator of the leptin response. In contrast to the current dogma, a longitudinal study of conditional Ift88 cilia mutant mice under different states of adiposity indicates that leptin resistance is present only when mutants are obese. Our studies show that caloric restriction leads to an altered anticipatory feeding behavior that temporarily abrogates the anorectic actions of leptin despite normalized circulating leptin levels. Interestingly, preobese Bbs4 mutant mice responded to the anorectic effects of leptin and did not display other phenotypes associated with defective leptin signaling. Furthermore, thermoregulation and activity measurements in cilia mutant mice are inconsistent with phenotypes previously observed in leptin deficient ob/ob mice. Collectively, these data indicate that cilia are not directly involved in leptin responses and that a defect in the leptin signaling axis is not the initiating event leading to hyperphagia and obesity associated with cilia dysfunction.

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Section: Resultssupporting

confidence: 72%

Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice

Berbari¹,

Pasek²,

Malarkey³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, rode diets exhibit increased body fat a weight regain because of pre stores. 45,46 These changes may b energy deficiency, which have be at the expense of lean tissues an NPY À / À mice showed no comp consequence of the increase in e associated increase in weight.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice

et al. 2012

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Background: Estrogen deficiency increases body weight or total and central adiposity and decreases energy expenditure. Hypothalamic neuropeptide Y (NPY) expression is altered by estrogen deficiency in rodents, but the long-term consequences on energy homeostasis are unknown. Objective: To investigate the role of NPY in the changes in energy expenditure and physical activity, as well as the associated changes in body weight and composition in response to short-term and long-term estrogen deficiency. Design: Sham and ovariectomy (OVX) operations were performed at 8 weeks of age in wild-type (WT) and NPY − / − mice. Energy expenditure, physical activity, body composition and weight, as well as food intake were measured at 10-18 days (short-term) and 46-54 days (long-term) after OVX. Results: OVX influences energy homeostasis differently at early compared with later time-points. At the early but not the late time point, OVX in WT mice reduced oxygen consumption and energy expenditure and tended to reduce resting metabolic rate. Interestingly, these effects of short-term estrogen deficiency were ablated by NPY deletion, with NPY − / − mice exhibiting significant increases in energy expenditure and resting metabolic rate. In addition to these hypermetabolic effects, OVX NPY − / − mice exhibited significantly lower body weight and whole-body fat mass relative to OVX WT controls at the short-term but not the long-term time point. Food intake and physical activity were unaltered by OVX, but NPY − / − mice exhibited significant reductions in these parameters relative to WT. Conclusion: The effects of estrogen deficiency to reduce energy metabolism are transient, and NPY is critical to this effect as well as the early OVX-induced obesity.

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“…Healthy mammals compensate for reduced caloric intake by reducing resting energy expenditure and/or activity. [42][43][44][45] When food restrictions are mild, saved energy may be preferentially directed to fat stores at the expense of fat free mass. 44,45 Indeed, liver and muscle mass in pair-fed mice were reduced.…”

Section: Discussionmentioning

confidence: 99%

“…[42][43][44][45] When food restrictions are mild, saved energy may be preferentially directed to fat stores at the expense of fat free mass. 44,45 Indeed, liver and muscle mass in pair-fed mice were reduced. Although cachectic mice significantly reduced their locomotor activity in our study, total energy expenditure in cachectic mice remained elevated compared to pair-fed mice.…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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Mild Calorie Restriction Induces Fat Accumulation in Female C57BL/6J Mice

Cited by 54 publications

References 40 publications

Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice

Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice

Neuropeptide Y mediates the short-term hypometabolic effect of estrogen deficiency in mice

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

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