Stimulation of brown adipose tissue activity in tumor-bearing rats

Oudart, Hugues; Calgari, Christiane; Andriamampandry, Margaret D.; Y, Le Maho; Малан, А.

doi:10.1139/y95-724

Cited by 26 publications

(13 citation statements)

References 22 publications

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“…In addition, during cachexia there is an important energetic imbalance. An increase in BAT thermogenesis has been described both in humans [16] and experimental animals [17]. Therefore, non-shivering thermogenesis due to either BAT activity or muscle increased thermogenesis (as suggested here) may be very important factors contributing to the decreased energy e¤ciency found in the cachectic state.…”

Section: Resultssupporting

confidence: 54%

“…Since cachexia tends to develop at a rather advanced stage of the neoplastic growth, preventing muscle waste in cancer patients is of a great potential clinical interest. Previous studies (See [15] for review) have shown that during cachectic states there is an increase in BAT thermogenesis both in humans [16] and experimental animals [17]. In addition, Roe et al [18] have shown that there is an increased oxygen consumption in leukaemic rats.…”

Section: Introductionmentioning

confidence: 99%

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Skeletal muscle UCP2 and UCP3 gene expression in a rat cancer cachexia model

et al. 1998

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Rats bearing the Yoshida AH-130 ascites hepatoma showed an increased expression of both uncoupling protein-2 (UCP2) (194%) and UCP3 (189%) mRNA levels in skeletal muscle 7 days after tumour inoculation. Interestingly, an even greater increase was observed in mRNA for both UCP2 (278%) and UCP3 (797%) in the pair-fed animals, suggesting that the increase in gene expression was the result of the anorexia associated with tumour burden. The results constitute the first report of UCP2 and UCP3 gene expression during cancer cachexia and agree to their possible role in the increase of energy expenditure associated with tumour growth.z 1998 Federation of European Biochemical Societies.

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Section: Resultssupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Skeletal muscle UCP2 and UCP3 gene expression in a rat cancer cachexia model

et al. 1998

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“…19,20 Increased thermogenic activity of BAT, as assessed by GDP binding, has been demonstrated in cancer cachexia models. 21,22 Our results suggested that inappropriate increased energy expenditure in BAT was associated with uremia-associated cachexia. Elevated BAT UCP-1 expression was attenuated by NBI-12i treatment.…”

Section: Discussionmentioning

confidence: 64%

Peripheral Administration of the Melanocortin-4 Receptor Antagonist NBI-12i Ameliorates Uremia-Associated Cachexia in Mice

Cheung

Kuo

Markison

et al. 2007

Journal of the American Society of Nephrology

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We have recently shown that genetic or pharmacological blockade of the melanocortin-4 receptor (MC4-R) attenuates uremia-associated cachexia. However, the potential clinical utility of this approach has been limited by the need to deliver a peptide MC4-R antagonist into the ventricles of the brain. NBI-12i is a recently developed small molecule MC4-R antagonist, with high affinity and selectivity that penetrates the central nervous system after peripheral administration. We tested whether NBI-12i would also be effective in attenuating uremia-associated cachexia in a mouse model. Intraperitoneal administration of NBI-12i stimulated food intake and weight gain in uremic mice. Furthermore, NBI-12i-treated uremic mice gained lean body mass, fat mass, and had a lower basal metabolic rate compared to vehicle-treated and diet-supplemented uremic mice, which lost both lean body mass and fat mass and had an increase in basal metabolic rate. We found that NBI-12i normalizes the expression of uncoupling protein, which is normally upregulated in uremic mice, and we speculate that this may contribute to the drug's protective effect. These data underscore the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and demonstrate the potential of peripheral administration of MC4-R antagonists as a novel therapeutic approach.

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“…Increased energy expenditure, which has been reported in both human and rodents with cancer cachexia (Hyltander et al . 1991; Oudart et al . 1995; Roe et al .…”

Section: Discussionmentioning

confidence: 99%

Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y

Chen

Taylor

Tisdale

et al. 2001

Journal of Neurochemistry

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Weight loss normally stimulates hunger, through mechanisms that include falls in circulating leptin and insulin, leading to stimulation of hypothalamic neuropeptide Y (NPY). Here, we investigated the leptin, insulin and NPY to clarify why hunger is suppressed in mice with severe cachexia due to the MAC16 adenocarcinoma. MAC16-bearing mice progressively lost weight (19% below controls) and fat (2 61%) over 16 days after tumour transplantation, while total food intake fell by 10%. Pair-fed mice showed less wasting, with ®nal weight being 9% and fat mass 25% below controls. Plasma leptin fell by 85% in MAC16 and 51% in pair-fed mice, in proportion to loss of fat. Plasma insulin was also reduced by 49% in MAC16 and 53% in pair-fed groups. Hypothalamic leptin receptor (OB-Rb) mRNA was signi®cantly increased in both MAC16 (1223%) and pair-fed (1192%) mice. Hypothalamic NPY mRNA was also signi®cantly raised in MAC16 (1152%) and pair-fed (199%) groups, showing negative correlations with plasma leptin and insulin, and a positive association with OBRb mRNA. In MAC16-induced cachexia, leptin production and hypothalamic OB-Rb and NPY expression are regulated appropriately in response to fat depletion. Therefore, suppression of hunger is probably due to tumour products that inhibit NPY transport or release, or that interfere with neuronal targets downstream of NPY. Keywords: cancer cachexia, hypothalamus, insulin, leptin, NPY, OB-Rb.Cachexia, marked loss of body protein and fat, is common in human gastrointestinal and pancreatic cancers and contributes greatly to morbidity and early death (Puccio and Nathanson 1997). An important paradox of cancer cachexia is that hunger is not stimulated following weight loss, as it is during starvation. Indeed, food intake is often decreased and is an important contributor to weight loss. Tissue catabolism and the suppression of hunger are presumed to be due to speci®c tumour products, as cachexia and hypophagia occur with very small tumour masses and in the absence of metastases. Some tumour products have been tentatively identi®ed in certain animal models of cancer cachexia, including proglucagon-derived peptides in the transplantable glucagonoma in the rat (Jensen et al. 1998), tumour necrosis factor-a (TNF-a) in an experimental transgenic tumour in mice (Oliff et al. 1987) and cytokines in rats with prostatic adenocarcinoma (Plata-Salaman et al. 1998). However, none of these has been convincingly implicated in human cancers, notably in the common gut-derived adenocarcinomas which are responsible for most of the clinical burden of cancer cachexia.Here, we have investigated peripheral and hypothalamic mechanisms of the cachexia syndrome in mice bearing the transplantable colonic adenocarcinoma, MAC16, which has pathogenic similarities to wasting in human gastrointestinal and pancreatic cancers (Bibby et al. 1987 Abbreviations used: ARC, arcuate nucleus; BSA, bovine serum antigen; CRF, corticotropin releasing factor; MC4-R, type-4 melanocortin receptor; a-MSH, a-melanocyte-stimula...

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Stimulation of brown adipose tissue activity in tumor-bearing rats

Cited by 26 publications

References 22 publications

Skeletal muscle UCP2 and UCP3 gene expression in a rat cancer cachexia model

Skeletal muscle UCP2 and UCP3 gene expression in a rat cancer cachexia model

Peripheral Administration of the Melanocortin-4 Receptor Antagonist NBI-12i Ameliorates Uremia-Associated Cachexia in Mice

Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y

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