Roles of Chronic Low-Grade Inflammation in the Development of Ectopic Fat Deposition

Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders.

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Visceral Adipose Tissue and Ectopic Fat Deposition

Handbook of Obesity ◽

10.1201/b16473-24 ◽

2014 ◽

pp. 237-248 ◽

Cited By ~ 1

Author(s):

Amalia Gastaldelli

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Fat Deposition ◽

Ectopic Fat ◽

Ectopic Fat Deposition ◽

Visceral Adipose

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Prostaglandin E2-EP4 Axis Promotes Lipolysis and Fibrosis in Adipose Tissue Leading to Ectopic Fat Deposition and Insulin Resistance

Cell Reports ◽

10.1016/j.celrep.2020.108265 ◽

2020 ◽

Vol 33 (2) ◽

pp. 108265 ◽

Cited By ~ 1

Author(s):

Tomoaki Inazumi ◽

Kiyotaka Yamada ◽

Naritoshi Shirata ◽

Hiroyasu Sato ◽

Yoshitaka Taketomi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Prostaglandin E2 ◽

Fat Deposition ◽

Ectopic Fat ◽

Ectopic Fat Deposition

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Downregulation of Adipose Tissue Fatty Acid Trafficking in Obesity: A Driver for Ectopic Fat Deposition?

Yearbook of Endocrinology ◽

10.1016/j.yend.2011.05.023 ◽

2011 ◽

Vol 2011 ◽

pp. 92-94

Author(s):

M.R. Ruth

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Fat Deposition ◽

Ectopic Fat ◽

Adipose Tissue Fatty Acid ◽

Tissue Fatty Acid ◽

Ectopic Fat Deposition

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Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18158004 ◽

2021 ◽

Vol 18 (15) ◽

pp. 8004

Author(s):

Wendy Hens ◽

Dirk Vissers ◽

Nick Verhaeghe ◽

Jan Gielen ◽

Luc Van Gaal ◽

...

Keyword(s):

Adipose Tissue ◽

Exercise Training ◽

Economic Analysis ◽

Controlled Trial ◽

Metabolic Health ◽

Overweight And Obesity ◽

Fat Deposition ◽

Hypocaloric Diet ◽

Ectopic Fat ◽

Ectopic Fat Deposition

Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: −18.88 cm², 95% CI −11.82 to −25.95), subcutaneous abdominal adipose tissue (SAT: −46.74 cm², 95% CI −29.76 to −63.18), epicardial fat (ECF: −14.50 cm³, 95% CI −10.9 to −18.98) and intrahepatic lipid content (IHL: −3.53%, 95% CI −1.72 to −5.32). Consequently, an “adapted” economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months.

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Mitochondrial oxidative stress in obesity: role of the mineralocorticoid receptor

Journal of Endocrinology ◽

10.1530/joe-18-0163 ◽

2018 ◽

Vol 238 (3) ◽

pp. R143-R159 ◽

Cited By ~ 10

Author(s):

Clara Lefranc ◽

Malou Friederich-Persson ◽

Roberto Palacios-Ramirez ◽

Aurelie Nguyen Dinh Cat

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Mineralocorticoid Receptor ◽

Bioactive Molecules ◽

Low Grade ◽

Metabolic Complications ◽

Mitochondrial Oxidative Stress ◽

Pathophysiological Role ◽

Low Grade Inflammation

Obesity is a multifaceted, chronic, low-grade inflammation disease characterized by excess accumulation of dysfunctional adipose tissue. It is often associated with the development of cardiovascular (CV) disorders, insulin resistance and diabetes. Under pathological conditions like in obesity, adipose tissue secretes bioactive molecules called ‘adipokines’, including cytokines, hormones and reactive oxygen species (ROS). There is evidence suggesting that oxidative stress, in particular, the ROS imbalance in adipose tissue, may be the mechanistic link between obesity and its associated CV and metabolic complications. Mitochondria in adipose tissue are an important source of ROS and their dysfunction contributes to the pathogenesis of obesity-related type 2 diabetes. Mitochondrial function is regulated by several factors in order to preserve mitochondria integrity and dynamics. Moreover, the renin–angiotensin–aldosterone system is over-activated in obesity. In this review, we focus on the pathophysiological role of the mineralocorticoid receptor in the adipose tissue and its contribution to obesity-associated metabolic and CV complications. More specifically, we discuss whether dysregulation of the mineralocorticoid system within the adipose tissue may be the upstream mechanism and one of the early events in the development of obesity, via induction of oxidative stress and mitochondrial dysfunction, thus impacting on systemic metabolism and the CV system.

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Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22042163 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2163

Author(s):

Yetirajam Rajesh ◽

Devanand Sarkar

Keyword(s):

Adipose Tissue ◽

Cancer Progression ◽

Metabolic Diseases ◽

Low Grade ◽

Metabolic Complications ◽

Endocrine Organ ◽

Nonalcoholic Fatty Liver ◽

Underlying Mechanisms ◽

Low Grade Inflammation ◽

Excessive Accumulation

Obesity is rapidly dispersing all around the world and is closely associated with a high risk of metabolic diseases such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), leading to carcinogenesis, especially hepatocellular carcinoma (HCC). It results from an imbalance between food intake and energy expenditure, leading to an excessive accumulation of adipose tissue (AT). Adipocytes play a substantial role in the tumor microenvironment through the secretion of several adipokines, affecting cancer progression, metastasis, and chemoresistance via diverse signaling pathways. AT is considered an endocrine organ owing to its ability to secrete adipokines, such as leptin, adiponectin, resistin, and a plethora of inflammatory cytokines, which modulate insulin sensitivity and trigger chronic low-grade inflammation in different organs. Even though the precise mechanisms are still unfolding, it is now established that the dysregulated secretion of adipokines by AT contributes to the development of obesity-related metabolic disorders. This review focuses on several obesity-associated adipokines and their impact on obesity-related metabolic diseases, subsequent metabolic complications, and progression to HCC, as well as their role as potential therapeutic targets. The field is rapidly developing, and further research is still required to fully understand the underlying mechanisms for the metabolic actions of adipokines and their role in obesity-associated HCC.

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Effect of 8 Weeks of Overfeeding on Ectopic Fat Deposition and Insulin Sensitivity: Testing the “Adipose Tissue Expandability” Hypothesis

Diabetes Care ◽

10.2337/dc14-0761 ◽

2014 ◽

Vol 37 (10) ◽

pp. 2789-2797 ◽

Cited By ~ 70

Author(s):

Darcy L. Johannsen ◽

Yourka Tchoukalova ◽

Charmaine S. Tam ◽

Jeffrey D. Covington ◽

Wenting Xie ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Fat Deposition ◽

Ectopic Fat ◽

Sensitivity Testing ◽

Ectopic Fat Deposition ◽

Adipose Tissue Expandability

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Duodenal adipose tissue is associated with obesity in baboons (Papio sp): a novel site of ectopic fat deposition in non-human primates

Acta Diabetologica ◽

10.1007/s00592-019-01286-w ◽

2019 ◽

Vol 56 (2) ◽

pp. 227-236 ◽

Cited By ~ 3

Author(s):

Paul B. Higgins ◽

Franco Folli ◽

Marcia C. R. Andrade ◽

Jaydee Foster ◽

Vicki Mattern ◽

...

Keyword(s):

Adipose Tissue ◽

Fat Deposition ◽

Ectopic Fat ◽

Ectopic Fat Deposition

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Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications

International Journal of Molecular Sciences ◽

10.3390/ijms20092358 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2358 ◽

Cited By ~ 104

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.

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