Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects

Rosenbaum, Michael; Vandenborne, Krista; Goldsmith, Rochelle L.; Simoneau, J. A.; Heymsfield, Steven B.; Joanisse, Denis R.; Hirsch, Jules; Murphy, Eleanor; Matthews, Dwight E.; Segal, Karen R.; Leibel, Rudolph L.

doi:10.1152/ajpregu.00474.2002

Cited by 208 publications

(278 citation statements)

References 38 publications

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“…Although cachectic mice significantly reduced their locomotor activity in our study, total energy expenditure in cachectic mice remained elevated compared to pair-fed mice. While differences in muscle work efficiency may have contributed to the differences in total energy expenditure, 46,47 these data suggest that resting energy expenditure in cachectic mice is abnormally elevated in early cachexia when food intake is taken into consideration.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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“…As skeletal muscle is an important site for energy conservation during starvation [53][54][55][56] , the control system underlying this adipose-specific control of thermogenesis could operate as a feedback loop between adipose tissue triglyceride stores and skeletal muscle metabolism. As depicted in Figure 4, it could comprise a sensor(s) of the state of depletion (or delayed expansion) of the fat stores, signal(s) dictating the suppression of thermogenesis as a function of the state of depletion of the fat stores, and an effector system mediating thermogenesis in skeletal muscle.…”

Section: The Thrifty Metabolism That Drives Catch-up Fat: Impact On Imentioning

confidence: 99%

Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance

Dulloo

2008

Best Practice & Research Clinical Endocrinology & Metab

101

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Catch-up growth early in life (after fetal, neonatal or infantile growth retardation) is a major risk factor for later obesity, type-2 diabetes and cardiovascular diseases. These risks are generally interpreted alongside teleological arguments that environmental exposures which hinder growth early in life lead to programming of 'thrifty mechanisms' that are adaptive during the period of limited nutrient supply (or growth constraint), but which increase risks for diseases during improved nutrition and catch-up growth later in life. This paper addresses this notion of 'thrifty mechanisms' in the light of evidence that catch-up growth is characterized by a disproportionately higher rate of fat gain relative to lean tissue gain, and that such preferential catch-up fat is in part driven by energy conservation mechanisms operating via suppressed thermogenesis. It provides a molecular-physiological framework which integrates emerging insights into mechanisms by which this thrifty 'catch-up fat' phenotype cross-links with insulin and leptin resistance.

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“…7,49 It is, however, not the aim of this paper to cover extensively EE regulatory systems, and readers can refer to several papers that have been written on the topic. 5,42,[48][49][50][51][52][53][54][55] Similarly, cellular mechanisms on the basis of human body thermogenesis, such as mitochondrial adenosine triphosphate synthesis efficiency, 56,57 uncoupling proteins 53,58 and their related increased muscle efficiency 59 will not be covered in this paper, as they have been directly addressed in their respective cited references. This conceptual paper will rather describe three conditions that have been associated to adaptive thermogenesis and that may thus represent limiting factors in weight loss, and confer a significant susceptibility to weight gain/regain in some individuals: body weight loss and regain cycles, organochlorine plasma concentration and hypoxia in severe form of obstructive sleep apnea.…”

Section: Determinant Factors Associated With the Adaptive Thermogenesismentioning

confidence: 99%

Clinical significance of adaptive thermogenesis

et al. 2007

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The epidemic of obesity is developing faster than the scientific understanding of an efficient way to overcome it, as reflected by the low success rate of short-and long-term weight loss interventions. From a clinical standpoint, this suggests that the body tends to defend a set point of possible genetic origin in the context of a weight-reducing program. As described in this paper, this limited therapeutic success may depend on adaptive thermogenesis, which represents in this case the decrease in energy expenditure (EE) beyond what could be predicted from the changes in fat mass or fat-free mass under conditions of standardized physical activity in response to a decrease in energy intake. This issue has been documented in recent studies that have shown in obese individuals adhering to a weight reduction program a greater than predicted decrease in EE, which in some cases was quantitatively sufficient to overcome the prescribed energy restriction, suggesting a role for adaptive thermogenesis in unsuccessful weight loss interventions and reduced body weight maintenance. As also discussed in this paper, this 'adaptive thermogenesis' can be influenced by environmental factors, which have not been frequently considered up to now. This is potentially the case for plasma organochlorine concentration and oxygen desaturation in obstructive sleep apnea syndrome. It is concluded that health professionals should be aware that in some vulnerable individuals, adaptive thermogenesis can be multicausal, and has the capacity to compensate, at least partly, for the prescribed energy deficit, possibly going beyond any good compliance of some patients.

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Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects

Cited by 208 publications

References 38 publications

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

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

Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance

Clinical significance of adaptive thermogenesis

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