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Article ; Online: Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis.

Arneson-Wissink, Paige C / Mendez, Heike / Pelz, Katherine / Dickie, Jessica / Bartlett, Alexandra Q / Worley, Beth L / Krasnow, Stephanie M / Eil, Robert / Grossberg, Aaron J

Journal of cachexia, sarcopenia and muscle

2024

Abstract: Background: Patients with pancreatic ductal adenocarcinoma (PDAC) often suffer from cachexia, a wasting syndrome that significantly reduces both quality of life and survival. Although advanced cachexia is associated with inflammatory signalling and ... ...

Abstract	Background: Patients with pancreatic ductal adenocarcinoma (PDAC) often suffer from cachexia, a wasting syndrome that significantly reduces both quality of life and survival. Although advanced cachexia is associated with inflammatory signalling and elevated muscle catabolism, the early events driving wasting are poorly defined. During periods of nutritional scarcity, the body relies on hepatic ketogenesis to generate ketone bodies, and lipid metabolism via ketogenesis is thought to protect muscle from catabolizing during nutritional scarcity. Methods: We developed an orthotopic mouse model of early PDAC cachexia in 12-week-old C57BL/6J mice. Murine pancreatic cancer cells (KPC) were orthotopically implanted into the pancreas of wild-type, IL-6 Results: Pre-cachectic PDAC mice did not preserve gastrocnemius muscle mass during 3-day food restriction (-13.1 ± 7.7% relative to food-restricted sham, P = 0.0117) and displayed impaired fatty acid oxidation during fasting, resulting in a hypoketotic state (ketogenic response to octanoate bolus, -83.0 ± 17.3%, P = 0.0328; Hmgcs2 expression, -28.3 ± 7.6%, P = 0.0004). PDAC human patients display impaired fasting ketones (-46.9 ± 7.1%, P < 0.0001) and elevated circulating interleukin-6 (IL-6) (12.4 ± 16.5-fold increase, P = 0.0001). IL-6 Conclusions: In early PDAC cachexia, muscle vulnerability to wasting is dependent on inflammation-driven metabolic reprogramming in the liver. PDAC suppresses lipid β-oxidation and impairs ketogenesis in the liver, which is reversed in genetically modified mouse models deficient in IL-6/STAT3 signalling or through ketogenic diet supplementation. This work establishes a direct link between skeletal muscle homeostasis and hepatic metabolism. Dietary and anti-inflammatory interventions that restore ketogenesis may be a viable preventative approach for pre-cachectic patients with pancreatic cancer.
Language	English
Publishing date	2024-04-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.13466
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing.

Huisman, Christian / Norgard, Mason A / Levasseur, Peter R / Krasnow, Stephanie M / van der Wijst, Monique G P / Olson, Brennan / Marks, Daniel L

Molecular metabolism

2022 Volume 58, Page(s) 101441

Abstract: Objective: Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. ... ...

Abstract	Objective: Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, the hypothalamus may play a central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location and attenuated blood-brain barrier. Furthermore, this region has a critical role in regulating appetite and metabolism. Methods: To provide a detailed analysis of the hypothalamic response to cachexia, we performed single-cell RNA-seq combined with RNA-seq of the medial basal hypothalamus (MBH) in a mouse model for pancreatic cancer. Results: We found many cell type-specific changes, such as inflamed endothelial cells, stressed oligodendrocyes and both inflammatory and moderating microglia. Lcn2, a newly discovered hunger suppressing hormone, was the highest induced gene. Interestingly, cerebral treatment with LCN2 not only induced many of the observed molecular changes in cachexia but also affected gene expression in food-intake decreasing POMC neurons. In addition, we found that many of the cachexia-induced molecular changes found in the hypothalamus mimic those at the primary tumor site. Conclusion: Our data reveal that multiple cell types in the MBH are affected by tumor-derived factors or host factors that are induced by tumor growth, leading to a marked change in the microenvironment of neurons critical for behavioral, metabolic, and neuroendocrine outputs dysregulated during cachexia. The mechanistic insights provided in this study explain many of the clinical features of cachexia and will be useful for future therapeutic development.
MeSH term(s)	Animals ; Cachexia/metabolism ; Endothelial Cells/metabolism ; Gene Regulatory Networks ; Hypothalamus/metabolism ; Mice ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Sequence Analysis, RNA ; Tumor Microenvironment ; Pancreatic Neoplasms
Language	English
Publishing date	2022-01-11
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2022.101441
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Article ; Online: Validation of automated body composition analysis using diagnostic computed tomography imaging in patients with pancreatic cancer.

Gunesch, Ali N / Sutton, Thomas L / Krasnow, Stephanie M / Deig, Christopher R / Sheppard, Brett C / Marks, Daniel L / Grossberg, Aaron J

American journal of surgery

2022 Volume 224, Issue 2, Page(s) 742–746

Abstract: Background: Sarcopenia is associated with complications and inferior oncologic outcomes in solid tumors. Axial computed tomography (CT) scans can be used to evaluate sarcopenia, however manual quantification is laborious. We sought to validate an ... ...

Abstract	Background: Sarcopenia is associated with complications and inferior oncologic outcomes in solid tumors. Axial computed tomography (CT) scans can be used to evaluate sarcopenia, however manual quantification is laborious. We sought to validate an automated method of quantifying muscle cross-sectional area (CSA) in patients with pancreatic adenocarcinoma (PDAC). Methods: Mid-L3 CT images from patients with PDAC were analyzed: CSAs of skeletal muscle (SM) were measured using manual segmentation and the software AutoMATiCA, and then compared with linear regression. Results: Five-hundred-twenty-five unique scans were analyzed. There was robust correlation between manual and automated segmentation for L3 CSA (R Conclusions: Automated muscle CSA measurement with AutoMATiCA is highly efficient and yields results highly correlated with manual measurement. These findings support the potential use of high-throughput sarcopenia analysis with abdominal CT scans for both clinical and research purposes.
MeSH term(s)	Adenocarcinoma/complications ; Adenocarcinoma/diagnostic imaging ; Body Composition ; Humans ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/diagnostic imaging ; Sarcopenia/complications ; Sarcopenia/diagnostic imaging ; Tomography, X-Ray Computed/methods ; Pancreatic Neoplasms
Language	English
Publishing date	2022-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2022.03.025
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Article ; Online: Identifying trajectories and predictors of chemotherapy-induced peripheral neuropathy symptoms, physical functioning, and falls across treatment and recovery in adults treated with neurotoxic chemotherapy: the PATTERN observational study protocol (NCT05790538).

Winters-Stone, Kerri M / Krasnow, Stephanie M / Horak, Fay B / Mancini, Martina / Cameron, Michelle H / Dieckmann, Nathan F / Stoyles, Sydnee A / Roeland, Eric J

BMC cancer

2023 Volume 23, Issue 1, Page(s) 1087

Abstract: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, ... ...

Abstract	Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, abnormal gait patterns, falls, and diminished quality of life. However, little is known regarding which patients are most likely to develop CIPN symptoms that impair mobility and increase fall risk, when this risk develops, or the optimal timing of early intervention efforts to mitigate the impact of CIPN on functioning and fall risk. This study will address these knowledge gaps by (1) characterizing trajectories of symptoms, functioning, and falls before, during, and after treatment in adults prescribed neurotoxic chemotherapy for cancer; and (2) determining the simplest set of predictors for identifying individuals at risk for CIPN-related functional decline and falls. Methods: We will enroll 200 participants into a prospective, observational study before initiating chemotherapy and up to 1 year after completing chemotherapy. Eligible participants are aged 40-85 years, diagnosed with stage I-III cancer, and scheduled to receive neurotoxic chemotherapy. We perform objective assessments of vibratory and touch sensation (biothesiometry, tuning fork, monofilament tests), standing and dynamic balance (quiet stance, Timed-Up-and-Go tests), and upper and lower extremity strength (handgrip dynamometry, 5-time repeated chair stand test) in the clinic at baseline, every 4-6 weeks during chemotherapy, and quarterly for 1 year post-chemotherapy. Participants wear devices that passively and continuously measure daily gait quality and physical activity for 1 week after each objective assessment and self-report symptoms (CIPN, insomnia, fatigue, dizziness, pain, cognition, anxiety, and depressive symptoms) and falls via weekly electronic surveys. We will use structural equation modeling, including growth mixture modeling, to examine patterns in trajectories of changes in symptoms, functioning, and falls associated with neurotoxic chemotherapy and then search for distinct risk profiles for CIPN. Discussion: Identifying simple, early predictors of functional decline and fall risk in adults with cancer receiving neurotoxic chemotherapy will help identify individuals who would benefit from early and targeted interventions to prevent CIPN-related falls and disability. Trial registration: This study was retrospectively registered with ClinicalTrials.gov (NCT05790538) on 3/30/2023.
MeSH term(s)	Adult ; Humans ; Antineoplastic Agents/adverse effects ; Hand Strength ; Neoplasms/complications ; Neurotoxicity Syndromes ; Observational Studies as Topic ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/diagnosis ; Peripheral Nervous System Diseases/drug therapy ; Prospective Studies ; Quality of Life ; Middle Aged ; Aged ; Aged, 80 and over
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-023-11546-2
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Article ; Online: Interleukin-1β signaling in fenestrated capillaries is sufficient to trigger sickness responses in mice.

Knoll, J Gabriel / Krasnow, Stephanie M / Marks, Daniel L

Journal of neuroinflammation

2017 Volume 14, Issue 1, Page(s) 219

Abstract: Background: The physiological and behavioral symptoms of sickness, including fever, anorexia, behavioral depression, and weight loss can be both beneficial and detrimental. These sickness responses are triggered by pro-inflammatory cytokines acting on ... ...

Abstract	Background: The physiological and behavioral symptoms of sickness, including fever, anorexia, behavioral depression, and weight loss can be both beneficial and detrimental. These sickness responses are triggered by pro-inflammatory cytokines acting on cells within the brain. Previous research demonstrates that the febrile response to peripheral insults depends upon prostaglandin production by vascular endothelial cells, but the mechanisms and specific cell type(s) responsible for other sickness responses remain unknown. The purpose of the present study was to identify which cells within the brain are required for sickness responses triggered by central nervous system inflammation. Methods: Intracerebroventricular (ICV) administration of 10 ng of the potent pro-inflammatory cytokine interleukin-1β (IL-1β) was used as an experimental model of central nervous system cytokine production. We examined which cells respond to IL-1β in vivo via fluorescent immunohistochemistry. Using multiple transgenic mouse lines expressing Cre recombinase under the control of cell-specific promoters, we eliminated IL-1β signaling from different populations of cells. Food consumption, body weight, movement, and temperature were recorded in adult male mice and analyzed by two-factor ANOVA to determine where IL-1β signaling is essential for sickness responses. Results: Endothelial cells, microglia, ependymal cells, and astrocytes exhibit nuclear translocation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) in response to IL-1β. Interfering with IL-1β signaling in microglia, endothelial cells within the parenchyma of the brain, or both did not affect sickness responses. Only mice that lacked IL-1β signaling in all endothelium including fenestrated capillaries lacked sickness responses. Conclusions: These experiments show that IL-1β-induced sickness responses depend on intact IL-1β signaling in blood vessels and suggest that fenestrated capillaries act as a critical signaling relay between the immune and nervous systems. Trial registration: Not applicable.
MeSH term(s)	Animals ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/metabolism ; Brain/drug effects ; Brain/metabolism ; Capillaries/drug effects ; Capillaries/pathology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Illness Behavior/drug effects ; Illness Behavior/physiology ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-1beta/metabolism ; Interleukin-1beta/toxicity ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	Interleukin-1beta
Language	English
Publishing date	2017-11-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-017-0990-7
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Article ; Online: Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing

Christian Huisman / Mason A. Norgard / Peter R. Levasseur / Stephanie M. Krasnow / Monique G.P. van der Wijst / Brennan Olson / Daniel L. Marks

Molecular Metabolism, Vol 58, Iss , Pp 101441- (2022)

2022

Abstract	Objective: Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, the hypothalamus may play a central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location and attenuated blood–brain barrier. Furthermore, this region has a critical role in regulating appetite and metabolism. Methods: To provide a detailed analysis of the hypothalamic response to cachexia, we performed single-cell RNA-seq combined with RNA-seq of the medial basal hypothalamus (MBH) in a mouse model for pancreatic cancer. Results: We found many cell type-specific changes, such as inflamed endothelial cells, stressed oligodendrocyes and both inflammatory and moderating microglia. Lcn2, a newly discovered hunger suppressing hormone, was the highest induced gene. Interestingly, cerebral treatment with LCN2 not only induced many of the observed molecular changes in cachexia but also affected gene expression in food-intake decreasing POMC neurons. In addition, we found that many of the cachexia-induced molecular changes found in the hypothalamus mimic those at the primary tumor site. Conclusion: Our data reveal that multiple cell types in the MBH are affected by tumor-derived factors or host factors that are induced by tumor growth, leading to a marked change in the microenvironment of neurons critical for behavioral, metabolic, and neuroendocrine outputs dysregulated during cachexia. The mechanistic insights provided in this study explain many of the clinical features of cachexia and will be useful for future therapeutic development.
Keywords	Cachexia models ; Pancreatic cancer ; Food intake regulation ; Endothelial inflammation ; scRNA-seq of the central nervous system ; Neuroinflammation ; Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neuropeptides in the pathophysiology and treatment of cachexia.

Krasnow, Stephanie M / Marks, Daniel L

Current opinion in supportive and palliative care

2010 Volume 4, Issue 4, Page(s) 266–271

Abstract: Purpose of review: Cachexia occurs in various inflammatory diseases and is characterized by weight loss and muscle wasting. Pro-inflammatory cytokines modulate the activity of neuropeptides and hormones that control energy homeostasis and/or illness ... ...

Abstract	Purpose of review: Cachexia occurs in various inflammatory diseases and is characterized by weight loss and muscle wasting. Pro-inflammatory cytokines modulate the activity of neuropeptides and hormones that control energy homeostasis and/or illness behaviors. This review summarizes recent (published within the past 18 months) literature regarding neuropeptides and hormones that have been implicated in the pathophysiology of cachexia, and that are likely to have therapeutic potential for preventing or reversing cachexia in various disease states. Recent findings: Hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons are downstream targets for pro-inflammatory cytokines. Genetic or pharmacological blockade of melanocortin receptor signaling preserves lean body mass and attenuates anorexia in experimental models of cachexia. Orally available melanocortin receptor antagonists have been developed and tested in cachectic animals with favorable results. Ghrelin and ghrelin mimetics increase appetite and preserve lean body mass in cachectic patients with diverse underlying diseases. Additional neuropeptide-expressing neurons in the hypothalamus (e.g., orexin neurons) might play a role in cachexia-associated lethargy. Summary: Promising outcomes from recent preclinical studies and/or early clinical trials with melanocortin receptor antagonists and ghrelin mimetics raise hopes that safe and effective anti-cachexia drugs will soon become available for widespread clinical use.
MeSH term(s)	Animals ; Cachexia/drug therapy ; Cachexia/metabolism ; Humans ; Neuropeptides/metabolism ; Neuropeptides/therapeutic use
Chemical Substances	Neuropeptides
Language	English
Publishing date	2010-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2633726-5
ISSN	1751-4266 ; 1751-4258
ISSN (online)	1751-4266
ISSN	1751-4258
DOI	10.1097/SPC.0b013e32833e48e7
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Article ; Online: Amplification and propagation of interleukin-1β signaling by murine brain endothelial and glial cells.

Krasnow, Stephanie M / Knoll, J Gabriel / Verghese, Santhosh Chakkaramakkil / Levasseur, Peter R / Marks, Daniel L

Journal of neuroinflammation

2017 Volume 14, Issue 1, Page(s) 133

Abstract: Background: During acute infections and chronic illnesses, the pro-inflammatory cytokine interleukin-1β (IL-1β) acts within the brain to elicit metabolic derangements and sickness behaviors. It is unknown which cells in the brain are the proximal ... ...

Abstract	Background: During acute infections and chronic illnesses, the pro-inflammatory cytokine interleukin-1β (IL-1β) acts within the brain to elicit metabolic derangements and sickness behaviors. It is unknown which cells in the brain are the proximal targets for IL-1β with respect to the generation of these illness responses. We performed a series of in vitro experiments to (1) investigate which brain cell populations exhibit inflammatory responses to IL-1β and (2) examine the interactions between different IL-1β-responsive cell types in various co-culture combinations. Methods: We treated primary cultures of murine brain microvessel endothelial cells (BMEC), astrocytes, and microglia with PBS or IL-1β, and then performed qPCR to measure inflammatory gene expression or immunocytochemistry to evaluate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. To evaluate whether astrocytes and/or BMEC propagate inflammatory signals to microglia, we exposed microglia to astrocyte-conditioned media and co-cultured endothelial cells and glia in transwells. Treatment groups were compared by Student's t tests or by ANOVA followed by Bonferroni-corrected t tests. Results: IL-1β increased inflammatory gene expression and NF-κB activation in primary murine-mixed glia, enriched astrocyte, and BMEC cultures. Although IL-1β elicited minimal changes in inflammatory gene expression and did not induce the nuclear translocation of NF-κB in isolated microglia, these cells were more robustly activated by IL-1β when co-cultured with astrocytes and/or BMEC. We observed a polarized endothelial response to IL-1β, because the application of IL-1β to the abluminal endothelial surface produced a more complex microglial inflammatory response than that which occurred following luminal IL-1β exposure. Conclusions: Inflammatory signals are detected, amplified, and propagated through the CNS via a sequential and reverberating signaling cascade involving communication between brain endothelial cells and glia. We propose that the brain's innate immune response differs depending upon which side of the blood-brain barrier the inflammatory stimulus arises, thus allowing the brain to respond differently to central vs. peripheral inflammatory insults.
MeSH term(s)	Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Brain/blood supply ; Brain/drug effects ; Brain/metabolism ; Cells, Cultured ; Coculture Techniques ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Female ; HEK293 Cells ; Humans ; Interleukin-1beta/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microvessels/drug effects ; Microvessels/metabolism ; Neuroglia/drug effects ; Neuroglia/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	Interleukin-1beta
Language	English
Publishing date	2017--01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1742-2094
ISSN (online)	1742-2094
DOI	10.1186/s12974-017-0908-4
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Article ; Online: Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia.

Olson, Brennan / Zhu, Xinxia / Norgard, Mason A / Levasseur, Peter R / Butler, John T / Buenafe, Abigail / Burfeind, Kevin G / Michaelis, Katherine A / Pelz, Katherine R / Mendez, Heike / Edwards, Jared / Krasnow, Stephanie M / Grossberg, Aaron J / Marks, Daniel L

Nature communications

2021 Volume 12, Issue 1, Page(s) 2057

Abstract: Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating ... ...

Abstract	Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator of appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, a devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models of pancreatic cancer, its expression is associated with reduced food consumption, and Lcn2 deletion is protective from cachexia-anorexia. Consistent with LCN2's proposed MC4R-dependent role in cancer-induced anorexia, pharmacologic MC4R antagonism mitigates cachexia-anorexia, while restoration of Lcn2 expression in the bone marrow is sufficient in restoring the anorexia feature of cachexia. Finally, we observe that LCN2 levels correlate with fat and lean mass wasting and is associated with increased mortality in patients with pancreatic cancer. Taken together, these findings implicate LCN2 as a pathologic mediator of appetite suppression during pancreatic cancer cachexia.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Animals ; Anorexia/blood ; Anorexia/complications ; Appetite ; Blood-Brain Barrier/pathology ; Bone Marrow/pathology ; Cachexia/blood ; Cachexia/complications ; Cell Line, Tumor ; Disease Models, Animal ; Feeding Behavior ; Female ; Gene Deletion ; Humans ; Lipocalin-2/blood ; Lipocalin-2/metabolism ; Male ; Mice, Knockout ; Middle Aged ; Models, Biological ; Muscles/pathology ; Neutrophils/pathology ; Organ Size ; Pancreatic Neoplasms/blood ; Pancreatic Neoplasms/complications ; Pancreatic Neoplasms/genetics ; Receptor, Melanocortin, Type 4/agonists ; Receptor, Melanocortin, Type 4/metabolism ; Up-Regulation ; Mice
Chemical Substances	Lipocalin-2 ; Receptor, Melanocortin, Type 4
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22361-3
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Article ; Online: Lipocalin 2 mediates appetite suppression during pancreatic cancer cachexia

Brennan Olson / Xinxia Zhu / Mason A. Norgard / Peter R. Levasseur / John T. Butler / Abigail Buenafe / Kevin G. Burfeind / Katherine A. Michaelis / Katherine R. Pelz / Heike Mendez / Jared Edwards / Stephanie M. Krasnow / Aaron J. Grossberg / Daniel L. Marks

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 15

Abstract: Lipocalin 2 (LCN2) has been recently identified as an endogenous regulator of appetite. Here, using pancreatic cancer as a model of cachexia, the authors demonstrate that LCN2 is a critical mediator of cancer-associated anorexia and may be ... ...

Abstract	Lipocalin 2 (LCN2) has been recently identified as an endogenous regulator of appetite. Here, using pancreatic cancer as a model of cachexia, the authors demonstrate that LCN2 is a critical mediator of cancer-associated anorexia and may be therapeutically targeted to improve patient outcomes.
Keywords	Science ; Q
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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