Cited by 156Regulation of Appetite and ObesityNutrition and Health in AgingMuscle Physiology and Disorders

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The central role of hypothalamic inflammation in the acute illness response and cachexia

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Burfeind, Kevin G., Michaelis, Katherine A., Marks, Daniel L.·2016·Seminars in Cell & Developmental Biology

DOI 10.1016/j.semcdb.2015.10.038PMC PMC4872506

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Abstract

When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes.

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Cancer-associated cachexia
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Antibody-mediated inhibition of GDF15–GFRAL activity reverses cancer cachexia in mice
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Authors: Burfeind, K. G., Michaelis, K. A., & Marks, D. L.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Marks, Daniel L.
ORCID: Burfeind, Kevin G.
Michaelis, Katherine A.
Marks, Daniel L.
Venue: Seminars in Cell & Developmental Biology
Publisher: Elsevier BV
Published: 2016-06
Volume: 54
Pages: 42-52
ISSN: 1084-9521 (ISSN-L)
DOI: 10.1016/j.semcdb.2015.10.038
PMC: PMC4872506
OpenAlex: W2189988755
Cited by: 156
References: 165
Citations by year: 2026: 7 · 2025: 20 · 2024: 13 · 2023: 15 · 2022: 18 · 2021: 24 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 6
FWCI: 0.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Seminars in Cell and Developmental Biology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA184324)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: hypothalamic inflammation, cachexia, fever, anorexia, fatigue, cytokines, chemokines, muscle atrophy, weight loss, chronic inflammation, neuroendocrine regulation, endothelial cells, peripheral blood leukocytes, infection, nutritional stress
MeSH terms: Animals, Cachexia, Humans, Hypothalamus, Inflammation, Models, Biological, Obesity, Muscle, Skeletal

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The central role of hypothalamic inflammation in the acute illness response and cachexia

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