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1.
Human Milk Drives the Intimate Interplay Between Gut Immunity and Adipose Tissue for Healthy Growth.
van den Elsen, LWJ, Verhasselt, V
Frontiers in immunology. 2021;:645415
Abstract
As the physiological food for the developing child, human milk is expected to be the diet that is best adapted for infant growth needs. There is also accumulating evidence that breastfeeding influences long-term metabolic outcomes. This review covers the potential mechanisms by which human milk could regulate healthy growth. We focus on how human milk may act on adipose tissue development and its metabolic homeostasis. We also explore how specific human milk components may influence the interplay between the gut microbiota, gut mucosa immunity and adipose tissue. A deeper understanding of these interactions may lead to new preventative and therapeutic strategies for both undernutrition and other metabolic diseases and deserves further exploration.
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2.
Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response.
Del Cornò, M, Varì, R, Scazzocchio, B, Varano, B, Masella, R, Conti, L
Cells. 2021;(7)
Abstract
Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.
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3.
Adipose Tissue Development and Expansion from the Womb to Adolescence: An Overview.
Orsso, CE, Colin-Ramirez, E, Field, CJ, Madsen, KL, Prado, CM, Haqq, AM
Nutrients. 2020;(9)
Abstract
Prevalence rates of pediatric obesity continue to rise worldwide. Adipose tissue (AT) development and expansion initiate in the fetus and extend throughout the lifespan. This paper presents an overview of the AT developmental trajectories from the intrauterine period to adolescence; factors determining adiposity expansion are also discussed. The greatest fetal increases in AT were observed in the third pregnancy trimester, with growing evidence suggesting that maternal health and nutrition, toxin exposure, and genetic defects impact AT development. From birth up to six months, healthy term newborns experience steep increases in AT; but a subsequent reduction in AT is observed during infancy. Important determinants of AT in infancy identified in this review included feeding practices and factors shaping the gut microbiome. Low AT accrual rates are maintained up to puberty onset, at which time, the pattern of adiposity expansion becomes sex dependent. As girls experience rapid increases and boys experience decreases in AT, sexual dimorphism in hormone secretion can be considered the main contributor for changes. Eating patterns/behaviors and interactions between dietary components, gut microbiome, and immune cells also influence AT expansion. Despite the plasticity of this tissue, substantial evidence supports that adiposity at birth and infancy highly influences its levels across subsequent life stages. Thus, a unique window of opportunity for the prevention and/or slowing down of the predisposition toward obesity, exists from pregnancy through childhood.
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4.
Dietary Regulation of Immunity.
Lee, AH, Dixit, VD
Immunity. 2020;(3):510-523
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Abstract
Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.
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The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.
Kiernan, K, MacIver, NJ
Frontiers in immunology. 2020;:622468
Abstract
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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The complement system is dysfunctional in metabolic disease: Evidences in plasma and adipose tissue from obese and insulin resistant subjects.
Moreno-Navarrete, JM, Fernández-Real, JM
Seminars in cell & developmental biology. 2019;:164-172
Abstract
The relationship among chronic low-grade inflammation, insulin resistance and other obesity-associated metabolic disturbances is increasingly recognized. The possible mechanisms that trigger these immunologic alterations remain to be fully understood. The complement system is a crucial element of immune defense system, being important in the activation of innate and adaptative immune response, promoting the clearance of apoptotic and damaged endogenous cells and participating in processes of tissue development, degeneration, and regeneration. Circulating components of the complement system appear to be dysregulated in obesity-associated metabolic disturbances. The activation of the complement system is also evident in adipose tissue from obese subjects, in association with subclinical inflammation and alterations in glucose metabolism. The possible contribution of some components of the complement system in the development of insulin resistance and obesity-associated metabolic disturbances, and the possible role of complement system in adipose tissue physiology is reviewed here. The modulation of the complement system could constitute a potential target in the pathophysiology and therapy of obesity and associated metabolic disease.
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7.
[Adipose tissue: immune function and alterations caused by obesity].
Vega-Robledo, GB, Rico-Rosillo, MG
Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993). 2019;(3):340-353
Abstract
The adipose tissue, which is currently viewed as an organ with neuroimmunoendocrine functions, participates in the homeostasis of the human organism. It has great plasticity and functional variability based on the intake of nutrients or to the increase or decrease of its tissue volume, which modifies both the function and the number of the cells that form it or reach it. The elements that are released abnormally by these cells, among other cytokines and adipokines, cause both local and systemic inflammation, mainly when they come from the visceral adipose tissue, and they can affect diverse organs like the liver and the cardio-vascular system. It has been pointed out that obesity entails a greater risk for developing inflammatory, metabolic, autoimmune, or allergic diseases, as well as alterations in scarring, and cancer.
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The Mesenteric Fat and Intestinal Muscle Interface: Creeping Fat Influencing Stricture Formation in Crohn's Disease.
Mao, R, Kurada, S, Gordon, IO, Baker, ME, Gandhi, N, McDonald, C, Coffey, JC, Rieder, F
Inflammatory bowel diseases. 2019;(3):421-426
Abstract
Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called "creeping fat") was described as a characteristic feature of Crohn's disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat-mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.
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Barriers to cancer nutrition therapy: excess catabolism of muscle and adipose tissues induced by tumour products and chemotherapy.
Schiessel, DL, Baracos, VE
The Proceedings of the Nutrition Society. 2018;(4):394-402
Abstract
Cancer-associated malnutrition is driven by reduced dietary intake and by underlying metabolic changes (such as inflammation, anabolic resistance, proteolysis, lipolysis and futile cycling) induced by the tumour and activated immune cells. Cytotoxic and targeted chemotherapies also elicit proteolysis and lipolysis at the tissue level. In this review, we summarise specific mediators and chemotherapy effects that provoke excess proteolysis in muscle and excess lipolysis in adipose tissue. A nutritionally relevant question is whether and to what degree these catabolic changes can be reversed by nutritional therapy. In skeletal muscle, tumour factors and chemotherapy drugs activate intracellular signals that result in the suppression of protein synthesis and activation of a transcriptional programme leading to autophagy and degradation of myofibrillar proteins. Cancer nutrition therapy is intended to ensure adequate provision of energy fuels and a complete repertoire of biosynthetic building blocks. There is some promising evidence that cancer- and chemotherapy-associated metabolic alterations may also be corrected by certain individual nutrients. The amino acids leucine and arginine provided in the diet at least partially reverse anabolic suppression in muscle, while n-3 PUFA inhibit the transcriptional activation of muscle catabolism. Optimal conditions for exploiting these anabolic and anti-catabolic effects are currently under study, with the overall aim of net improvements in muscle mass, functionality, performance status and treatment tolerance.
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10.
Contribution of Adipose Tissue to Development of Cancer.
Cozzo, AJ, Fuller, AM, Makowski, L
Comprehensive Physiology. 2017;(1):237-282
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Abstract
Solid tumor growth and metastasis require the interaction of tumor cells with the surrounding tissue, leading to a view of tumors as tissue-level phenomena rather than exclusively cell-intrinsic anomalies. Due to the ubiquitous nature of adipose tissue, many types of solid tumors grow in proximate or direct contact with adipocytes and adipose-associated stromal and vascular components, such as fibroblasts and other connective tissue cells, stem and progenitor cells, endothelial cells, innate and adaptive immune cells, and extracellular signaling and matrix components. Excess adiposity in obesity both increases risk of cancer development and negatively influences prognosis in several cancer types, in part due to interaction with adipose tissue cell populations. Herein, we review the cellular and noncellular constituents of the adipose "organ," and discuss the mechanisms by which these varied microenvironmental components contribute to tumor development, with special emphasis on obesity. Due to the prevalence of breast and prostate cancers in the United States, their close anatomical proximity to adipose tissue depots, and their complex epidemiologic associations with obesity, we particularly highlight research addressing the contribution of adipose tissue to the initiation and progression of these cancer types. Obesity dramatically modifies the adipose tissue microenvironment in numerous ways, including induction of fibrosis and angiogenesis, increased stem cell abundance, and expansion of proinflammatory immune cells. As many of these changes also resemble shifts observed within the tumor microenvironment, proximity to adipose tissue may present a hospitable environment to developing tumors, providing a critical link between adiposity and tumorigenesis. © 2018 American Physiological Society. Compr Physiol 8:237-282, 2018.