Anorexia induced by chronic central administration of cytokines at estimated pathophysiological concentrations

Plata‐Salamán, Carlos R.; Sonti, Gayatri; Borkoski, J. P.; Wilson, Charlie D.; Ffrench‐Mullen, J. M. H.

doi:10.1016/0031-9384(96)00148-5

Cited by 109 publications

(58 citation statements)

References 30 publications

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“…Neutralization of these factors by genetic or pharmacological methods leads to attenuation of cachexia (Plata-Salaman, 1998;Plata-Salaman and Borkoski, 1994;Sherry et al, 1989;Vallieres and Rivest, 1997;Yasumoto et al, 1995). Finally, chronic infusion of IL-lp or TNF-cx causes anorexia, rapid weight loss, and catabolism of body protein stores, analogous to the state observed with chronic illness Plata-Salaman et al, 1996).…”

Section: A the Role Of Cytokinesmentioning

confidence: 90%

Central Melanocortins and the Regulation of Weight During Acute and Chronic Disease

Marks

Cone

2001

Recent Progress in Hormone Research

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Recent advances in our understanding of the regulation of body weight, appetite, and metabolic rate have highlighted the role of the adipose-derived hormone leptin and its receptor as fundamental modulators of these processes. Investigations of the neural targets for leptin action -as well as characterization of the agouti obesity syndrome -have, in turn, led to the discovery of fundamental neural pathways involved in the central regulation of energy homeostasis. In particular, the central melanocortin system has been shown to regulate appetite and metabolic rate in rodents; mutations in this system have been demonstrated to result in obesity in humans. Overall, the melanocortin system appears to function as a bidirectional rheostat in the regulation of energy intake and expenditure in rodents and potentially in humans. The first section of this chapter will focus on the development of our understanding of melanocortin physiology in the context of obesity. In particular, recent data regarding the interplay between melanocortin and neuropeptide Y (NPY) signaling at a cellular level will be discussed. The following section will discuss the hypothesis that melanocortin signaling plays a role in pathological weight loss and hypermetabolism observed in murine cachexia models. The potential role of this system in integrating a variety of anorexic and cachexic signals, as well as the potential for its pharmacological manipulation in the treatment of human cachexia, will be discussed. I. The Central Melanocortin System and Energy Homeostasis A. INTRODUCTIONThe last decade has witnessed significant advances in our understanding of energy homeostasis and regulation of body weight. The recent cloning and characterization of the genes responsible for obesity syndromes in the mouse -fatty, tubby, obesity, diabetes, and agouti -had led to our current understanding of the role of the adipocyte hormone leptin and its receptor in the feedback regulation of appetite and metabolic rate (Chua et al., 1996;Tartaglia et al., 1995;Zhang et al., 1997). Furthermore, we have started to unravel the neuronal pathways that mediate many of the effects of leptin and exert central control over processes fundamental to the intake, use, and storage of body fuels. In particular, the cloning of the agouti gene (Bultman et al., 1992;Miller et al., 1993) and the discovery of its mechanism of action (Fan et al., 1997;Huszar et al., 1997;Lu et al., 1994) led to the identification of a set of neuronal pathways that we will refer to as the melanocortin system. In general, the melanocortin system can be detined as the hypothalamic and brainstem neurons expressing pro-opiomelanocortin (POMC), the hypothalamic neurons coexpressing neuropeptide Y (NPY) and the melanocortin antagonist agouti-related protein (AGRP), and the neurons downstream of these systems. For the purposes of this chapter, these downstream neurons will be defined by the presence of the two primary central melanocortin receptors, melanocortin 3 receptor (MC3-R) (Roselli-Rehfuss et ...

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Section: A the Role Of Cytokinesmentioning

confidence: 90%

Central Melanocortins and the Regulation of Weight During Acute and Chronic Disease

Marks

Cone

2001

Recent Progress in Hormone Research

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“…Inflammation is associated with increase in body temperature; an increase of 1°C equates to a 13% increase in the basal metabolism (Kluger, 1978). The increase in the concentrations of proinflammatory cytokines such as TNF-a and IL-1 ß have been shown to decrease feed consumption (Plata-Salamán et al, 1996), rates of BW gain, and efficiency of feed utilization (Evock-Clover et al, 1997;Steiger et al, 1999). Thus, endotoxin-assoeiated inflammation results in an estimated 30% increase in energetic costs and leads to a significant negative nitrogen balance because of protein breakdown and deereased BW gain (Lochmiller and Deerenberg, 2000).…”

Section: Implications Of Intestinal Endotoxin and Inflammationmentioning

confidence: 98%

GROWTH AND DEVELOPMENT SYMPOSIUM: Endotoxin, inflammation, and intestinal function in livestock1,2

Mani

Weber

Baumgard

et al. 2012

Journal of Animal Science

154

131

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Endotoxin, also referred to as lipopolysaccharide (LPS), can stimulate localized or systemic inflammation via the activation of pattern recognition receptors. Additionally, endotoxin and inflammation can regulate intestinal epithelial function by altering integrity, nutrient transport, and utilization. The gastrointestinal tract is a large reservoir of both gram-positive and gram-negative bacteria, of which the gram-negative bacteria serve as a source of endotoxin. Luminal endotoxin can enter circulation via two routes: 1) nonspecific paracellular transport through epithelial cell tight junctions, and 2) transcellular transport through lipid raft membrane domains involving receptor-mediated endocytosis. Paracellular transport of endotoxin occurs through dissociation of tight junction protein complexes resulting in reduced intestinal barrier integrity, which can be a result of enteric disease, inflammation, or environmental and metabolic stress. Transcellular transport, via specialized membrane regions rich in glycolipids, sphingolipids, cholesterol, and saturated fatty acids, is a result of raft recruitment of endotoxin-related signaling proteins leading to endotoxin signaling and endocytosis. Both transport routes and sensitivity to endotoxin may be altered by diet and environmental and metabolic stresses. Intestinal-derived endotoxin and inflammation result in suppressed appetite, activation of the immune system, and partitioning of energy and nutrients away from growth toward supporting the immune system requirements. In livestock, this leads to the suppression of growth, particularly suppression of lean tissue accretion. In this paper, we summarize the evidence that intestinal transport of endotoxin and the subsequent inflammation leads to decrease in the production performance of agricultural animals and we present an overview of endotoxin detoxification mechanisms in livestock.

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“…Neutralization of these factors by genetic or pharmacological methods leads to attenuation of cachexia [26,27]. Chronic infusion of IL-1b or TNFa causes anorexia, rapid weight loss and catabolism of body protein stores, analogous to the state observed with chronic illness [28]. Tumor-bearing animals frequently die from cachexia and exhaustion of metabolic fuels.…”

Section: The Role Of Cytokines In Cachexia Of Chronic Illnessmentioning

confidence: 99%

Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease

et al. 2005

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Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies.

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Anorexia induced by chronic central administration of cytokines at estimated pathophysiological concentrations

Cited by 109 publications

References 30 publications

Central Melanocortins and the Regulation of Weight During Acute and Chronic Disease

Central Melanocortins and the Regulation of Weight During Acute and Chronic Disease

GROWTH AND DEVELOPMENT SYMPOSIUM: Endotoxin, inflammation, and intestinal function in livestock1,2

Orexigenic and anorexigenic mechanisms in the control of nutrition in chronic kidney disease

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