A Tale of Three Systems: Toward a Neuroimmunoendocrine Model of Obesity

2021 ◽  
Vol 37 (1) ◽  
pp. 549-573
Author(s):  
Conan J.O. O'Brien ◽  
Emma R. Haberman ◽  
Ana I. Domingos
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Neural Circuitry ◽  
Leptin Resistance ◽  
Direct Role ◽  
Adipose Tissues ◽  
Adipose Tissue Macrophages ◽  
Prevalence Of Obesity ◽  
Established Role

The prevalence of obesity is on the rise. What was once considered a simple disease of energy imbalance is now recognized as a complex condition perpetuated by neuro- and immunopathologies. In this review, we summarize the current knowledge of the neuroimmunoendocrine mechanisms underlying obesity. We examine the pleiotropic effects of leptin action in addition to its established role in the modulation of appetite, and we discuss the neural circuitry mediating leptin action and how this is altered with obesity, both centrally (leptin resistance) and in adipose tissues (sympathetic neuropathy). Finally, we dissect the numerous causal and consequential roles of adipose tissue macrophages in obesity and highlight recent key studies demonstrating their direct role in organismal energy homeostasis.

scholarly journals Adipose gene expression profiles reveal novel insights into the adaptation of northern Eurasian semi-domestic reindeer (Rangifer tarandus)

2021 ◽  
Author(s):  
Melak Weldenegodguad ◽  
Kisun Pokharel ◽  
Laura Niiranen ◽  
Päivi Soppela ◽  
Innokentyi Ammosov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Rangifer Tarandus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Northern Eurasia ◽  
Adipose Tissues ◽  
Arctic Conditions

AbstractReindeer (Rangifer tarandus) are semi-domesticated animals adapted to the challenging arctic conditions of northern Eurasia. Adipose tissues play a crucial role in animals living in northern environments by altering gene expression in their tissues to regulate energy homeostasis and thermogenic activity. Here, we performed transcriptome profiling by RNA sequencing of adipose tissues from three different anatomical depots: metacarpal (bone marrow), perirenal, and prescapular fat in Finnish and Even reindeer (in Sakha) during two seasonal time points (spring and winter). On average 36.5 million pair-ended clean reads were obtained for each sample, and a total of 16,362 genes were expressed in our data. Gene expression profiles in metacarpal tissue were distinct and clustered separately from perirenal and prescapular adipose tissues. Notably, metacarpal adipose tissue appeared to have a significant role in the regulation of the energy metabolism of reindeer in spring when their nutritional condition is poor after winter. During spring, when the animals are in less optimal condition, genes associated with the immune system (e.g., CCL2, CCL11, CXCL14, IGSF3, IGHM, IGLC7, IGKC, JCHAIN, and IGSF10) were upregulated in the perirenal and prescapular adipose tissue, while genes involved in energy metabolism (e.g., ACOT2, APOA1, ANGPTL1, ANGPTL8, ELOVL7, MSMO1, PFKFB1, and ST3GAL6) were upregulated in metacarpal tissue. Even reindeer harboured relatively fewer significantly differentially expressed genes than Finnish reindeer, irrespective of the season, possibly owing to climatic and management differences. Moreover, blood and tissue parameters reflecting general physiological and metabolic status showed less seasonal variation in Even reindeer than in Finnish reindeer. This study identified adipose candidate genes potentially involved in immune response, fat deposition, energy metabolism, development, cell growth, and organogenesis. Taken together, this study provides new information on the mechanisms by which reindeer adapt to less optimal arctic conditions.

Selective Leptin Resistance in Brain but Not in Adipose-Tissue Macrophages Following High-Fat Feeding

2011 ◽  
pp. P2-429-P2-429
Author(s):  
Diana Athonvarangku ◽  
Kehao Zhang ◽  
Weijie Li ◽  
Preeti Kishore ◽  
Meredith Hawkins
Keyword(s):  
Adipose Tissue ◽  
Leptin Resistance ◽  
High Fat ◽  
Adipose Tissue Macrophages ◽  
Fat Feeding

scholarly journals 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue

2012 ◽  
Vol 216 (2) ◽  
pp. 265-271 ◽  
Author(s):  
Juan Kong ◽  
Yunzi Chen ◽  
Guojun Zhu ◽  
Qun Zhao ◽  
Yan Chun Li
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Ex Vivo ◽  
Critical Role ◽  
Dependent Manner ◽  
Adipose Tissues ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Leptin Expression

Leptin is an adipose tissue-derived hormone that plays a critical role in energy homeostasis. Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear. Leptin expression and secretion was reduced in vitamin D receptor (VDR)-null mice and increased in transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression. To address this question, we determined the effect of vitamin D on leptin expressionin vivoandex vivo. One-week treatment of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR-null mice, and leptin upregulation induced by 1,25-dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D stimulates adipose leptin production in a VDR-dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression.

scholarly journals The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4924 ◽  
Author(s):  
Lee ◽  
Park ◽  
Oh ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Brown Adipose

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

scholarly journals On the role of macrophages in the control of adipocyte energy metabolism

2019 ◽  
Vol 8 (6) ◽  
pp. R105-R121 ◽  
Author(s):  
Michaela Keuper
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Current Knowledge ◽  
Human Adipose Tissue ◽  
White Adipocytes ◽  
Secreted Factors ◽  
Adipose Tissue Macrophages

The crosstalk between macrophages (MΦ) and adipocytes within white adipose tissue (WAT) influences obesity-associated insulin resistance and other associated metabolic disorders, such as atherosclerosis, hypertension and type 2 diabetes. MΦ infiltration is increased in WAT during obesity, which is linked to decreased mitochondrial content and activity. The mechanistic interplay between MΦ and mitochondrial function of adipocytes is under intense investigation, as MΦ and inflammatory pathways exhibit a pivotal role in the reprogramming of WAT metabolism in physiological responses during cold, fasting and exercise. Thus, the underlying immunometabolic pathways may offer therapeutic targets to correct obesity and metabolic disease. Here, I review the current knowledge on the quantity and the quality of human adipose tissue macrophages (ATMΦ) and their impact on the bioenergetics of human adipocytes. The effects of ATMΦ and their secreted factors on mitochondrial function of white adipocytes are discussed, including recent research on MΦ as part of an immune signaling cascade involved in the ‘browning’ of WAT, which is defined as the conversion from white, energy-storing adipocytes into brown, energy-dissipating adipocytes.

scholarly journals PPARs, Obesity, and Inflammation

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Rinke Stienstra ◽  
Caroline Duval ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Vascular Wall ◽  
Peroxisome Proliferator ◽  
Proinflammatory Mediators ◽  
Inflammatory Status ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors

The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.

scholarly journals Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1383 ◽  
Author(s):  
Ziyi Song ◽  
Alus Xiaoli ◽  
Fajun Yang
Keyword(s):  
Energy Homeostasis ◽  
De Novo ◽  
Current Knowledge ◽  
De Novo Lipogenesis ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Therapeutic Opportunity ◽  
Regulate Energy Metabolism

De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. Dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases. Thus, the lipogenic pathway may provide a new therapeutic opportunity for combating various pathological conditions that are associated with dysregulated lipid metabolism. Hepatic DNL has been well documented, but lipogenesis in adipocytes and its contribution to energy homeostasis and insulin sensitivity are less studied. Recent reports have gained significant insights into the signaling pathways that regulate lipogenic transcription factors and the role of DNL in adipose tissues. In this review, we will update the current knowledge of DNL in white and brown adipose tissues with the focus on transcriptional, post-translational, and central regulation of DNL. We will also summarize the recent findings of adipocyte DNL as a source of some signaling molecules that critically regulate energy metabolism.

scholarly journals Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications

2019 ◽  
Vol 20 (9) ◽  
pp. 2358 ◽  
Author(s):  
Michele Longo ◽  
Federica Zatterale ◽  
Jamal Naderi ◽  
Luca Parrillo ◽  
Pietro Formisano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Tissue Expansion ◽  
Low Grade ◽  
Metabolic Complications ◽  
Visceral Adipose ◽  
Subcutaneous Adipose ◽  
Low Grade Inflammation

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.

scholarly journals Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 62 ◽  
Author(s):  
Sebastiano Andò ◽  
Luca Gelsomino ◽  
Salvatore Panza ◽  
Cinzia Giordano ◽  
Daniela Bonofiglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Epidemiological Evidence ◽  
Tissue Mass ◽  
Prevalence Of Obesity ◽  
Total Adipose Tissue ◽  
Excessive Adiposity ◽  
Risk Prognosis

The prevalence of obesity has been steadily increasing over the past few decades in several developed and developing countries, with resultant hazardous health implications. Substantial epidemiological evidence has shown that excessive adiposity strongly influences risk, prognosis, and progression of various malignancies, including breast cancer. Indeed, it is now well recognized that obesity is a complex physiologic state associated with multiple molecular changes capable of modulating the behavior of breast tumor cells as well of the surrounding microenvironment. Particularly, insulin resistance, hyperactivation of insulin-like growth factor pathways, and increased levels of estrogen due to aromatization by the adipose tissue, inflammatory cytokines, and adipokines contribute to breast cancerogenesis. Among adipokines, leptin, whose circulating levels increase proportionally to total adipose tissue mass, has been identified as a key member of the molecular network in obesity. This review summarizes the current knowledge on the epidemiological link existing between obesity and breast cancer and outlines the molecular mechanisms underlying this connection. The multifaceted role of the obesity adipokine leptin in this respect is also discussed.

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