Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.

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Adipokine Contribution to the Pathogenesis of Osteoarthritis

Mediators of Inflammation ◽

10.1155/2017/5468023 ◽

2017 ◽

Vol 2017 ◽

pp. 1-26 ◽

Cited By ~ 58

Author(s):

Daniel Azamar-Llamas ◽

Gabriela Hernández-Molina ◽

Bárbara Ramos-Ávalos ◽

Janette Furuzawa-Carballeda

Keyword(s):

Adipose Tissue ◽

Risk Factor ◽

Weight Bearing ◽

Epidemiological Studies ◽

Overweight And Obesity ◽

Cartilage Explants ◽

Metabolic Factors ◽

Physiological Mechanisms ◽

Cartilage Homeostasis ◽

And Cartilage

Recent studies have shown that overweight and obesity play an important role in the development of osteoarthritis (OA). However, joint overload is not the only risk factor in this disease. For instance, the presence of OA in non-weight-bearing joints such as the hand suggests that metabolic factors may also contribute to its pathogenesis. Recently, white adipose tissue (WAT) has been recognized not only as an energy reservoir but also as an important secretory organ of adipokines. In this regard, adipokines have been closely associated with obesity and also play an important role in bone and cartilage homeostasis. Furthermore, drugs such as rosuvastatin or rosiglitazone have demonstrated chondroprotective and anti-inflammatory effects in cartilage explants from patients with OA. Thus, it seems that adipokines are important factors linking obesity, adiposity, and inflammation in OA. In this review, we are focused on establishing the physiological mechanisms of adipokines on cartilage homeostasis and evaluating their role in the pathophysiology of OA based on evidence derived from experimental research as well as from clinical-epidemiological studies.

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Genetic predictors of obesity development

Obesity and metabolism ◽

10.14341/omet201627-13 ◽

2016 ◽

Vol 13 (2) ◽

pp. 7-13 ◽

Cited By ~ 6

Author(s):

Svetlana V. Borodina ◽

Kamila M. Gapparova ◽

Zainudin M. Zainudiniv ◽

Olga N. Grigorian

Keyword(s):

Physical Activity ◽

Environmental Factors ◽

Genetic Factors ◽

Endocrine System ◽

Current Data ◽

Overweight And Obesity ◽

Obese People ◽

Direct Role ◽

Sugary Drinks ◽

The Impact

The most common reasons that cause obesity are eating disorders (overeating), genetic predisposition, sedentary lifestyle (lack of exercise), disorders of the endocrine system, and environmental factors. There is evidence of an obvious relationship of high consumption of sugary drinks and weight gain. Since 1990, there has been considerable growth in the number of obese people in the first place associated with the promotion of soft drinks. According to a study in Finnish diabetes prevention average physical activity and change of diet (1200-1800 kcal) of total fat intake with less than 30% saturated fat, including less than 10%, leading to long-term loss of excess weight (within 4 years). Many studies have demonstrated the impossibility of a single template approach to the determination of optimal diets for patients with overweight and obesity which has been shown in various studies on gene polymorphisms are associated with obesity, and their interaction. This article provides an overview of current data on the genetics of obesity covering the main provisions of the study of candidate genes, such as PPARG, FABP2, ADRB 2, ADRB3. The role nutrigenetics in the creation of individual programs of weight control and weight loss. But the question of the direct role of genetic factors in the development of obesity remains controversial, since one can not ignore the impact of environmental factors, such as lifestyle, diet, physical activity, stress, and harmful habits. To understand the mechanism of the relationship between genetic factors, environmental factors, and obesity, one needs to carry out research not only on the population level, but also in certain groups of people (ethnic, racial, age).

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Pro-inflammatory effects of DEHP in SGBS-derived adipocytes and THP-1 macrophages

Scientific Reports ◽

10.1038/s41598-021-85119-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kristina Schaedlich ◽

Laura-Sophie Beier ◽

Judith Kolbe ◽

Martin Wabitsch ◽

Jana Ernst

Keyword(s):

Adipose Tissue ◽

Energy Homeostasis ◽

Overweight And Obesity ◽

Environmental Chemicals ◽

Low Grade ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Secreted Factors ◽

The Impact ◽

Dehp Exposure

AbstractIn the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson–Golabi–Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)–d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

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Obesity and Pancreatic Cancer: Insight into Mechanisms

Cancers ◽

10.3390/cancers13205067 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5067

Author(s):

Guido Eibl ◽

Enrique Rozengurt

Keyword(s):

Pancreatic Cancer ◽

Adipose Tissue ◽

Risk Factor ◽

Cancer Development ◽

Fibroblast Growth Factor 21 ◽

Adipose Tissue Inflammation ◽

Lipocalin 2 ◽

Tissue Inflammation ◽

Chronic Progressive Disease ◽

The Impact

The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.

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Obesity-related proliferative diseases: the interaction between adipose tissue and estrogens in post-menopausal women

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2015-0002 ◽

2015 ◽

Vol 21 (1) ◽

Cited By ~ 3

Author(s):

Valentina Vicennati ◽

Silvia Garelli ◽

Eleonora Rinaldi ◽

Sara Rosetti ◽

Guido Zavatta ◽

...

Keyword(s):

Adipose Tissue ◽

Cancer Risk ◽

Epidemiological Studies ◽

Tumor Promoter ◽

Cancer Development ◽

Focus Attention ◽

Menopausal Women ◽

Post Menopausal ◽

Obesity And Cancer ◽

The Relationship

AbstractEpidemiological studies have shown that overweight and cancer are closely related, even though obesity alone does not apparently heighten cancer risk by the same amount. Given the low overall risk of all cancers with obesity, it is unlikely that obesity alone causes cancer, but should instead be considered as a tumor promoter. There are three main hypotheses that could explain how obesity might contribute to cancer development and growth: the inflammatory cytokines from adipose tissue hypothesis, the insulin resistance and hyperinsulinemia hypothesis, and the unopposed estrogen cancer hypothesis. The link between obesity and cancer is that adipocytes constitute a major component of the tumor microenvironment for breast and abdominally metastasizing cancers, promoting tumor growth. This review will mainly focus attention on the relationship between adipose tissue, estrogens, and cancer risk.

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MECHANISMS OF ENDOCRINOLOGY: Mechanisms of disease: the endocrinology of obstructive sleep apnoea

Acta Endocrinologica ◽

10.1530/eje-18-0411 ◽

2019 ◽

Vol 180 (3) ◽

pp. R91-R125 ◽

Cited By ~ 4

Author(s):

Aikaterini Lavrentaki ◽

Asad Ali ◽

Brendan G Cooper ◽

Abd A Tahrani

Keyword(s):

Obstructive Sleep Apnoea ◽

Negative Impact ◽

Endocrine System ◽

Epidemiological Studies ◽

Sleep Apnoea ◽

Upper Airways ◽

Obstructive Sleep ◽

Bidirectional Relationship ◽

Randomised Controlled ◽

The Impact

Obstructive sleep apnoea (OSA) is a common disorder that is associated with serious comorbidities with a negative impact on quality of life, life expectancy and health costs. As OSA is related to obesity and is associated with sleep disruption, increased inflammation and oxidative stress, it is not surprising that OSA has an impact on the secretion of multiple hormones and is implicated in the development of many endocrine conditions. On the other hand, many endocrine conditions that can affect obesity and/or upper airways anatomy and stability have been implicated in the development or worsening of OSA. This bidirectional relationship between OSA and the endocrine system has been increasingly recognised in experimental and epidemiological studies and there are an increasing number of studies examining the effects of OSA treatment on endocrine conditions and vice versa. In this review article, we will critically appraise and describe the impact of OSA on the endocrine system including obesity, dysglycaemia, the pituitary, the thyroid, the adrenals, the reproductive system and the bones. In each section, we will assess whether a bidirectional relationship exists, and we will describe the potential underlying mechanisms. We have focused more on recent studies and randomised controlled trials where available and attempted to provide the information within clinical context and relevance.

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Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression

Nutrients ◽

10.3390/nu13113902 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3902

Author(s):

Ozan Berk Imir ◽

Alanna Zoe Kaminsky ◽

Qian-Ying Zuo ◽

Yu-Jeh Liu ◽

Ratnakar Singh ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

High Fat Diet ◽

Flame Retardants ◽

Epidemiological Studies ◽

Cancer Development ◽

Prostate Cancer Progression ◽

High Fat ◽

The Impact

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals utilized in various industrial settings and include products such as flame retardants, artificial film-forming foams, cosmetics, and non-stick cookware, among others. Epidemiological studies suggest a link between increased blood PFAS levels and prostate cancer incidence, but the mechanism through which PFAS impact cancer development is unclear. To investigate the link between PFAS and prostate cancer, we evaluated the impact of metabolic alterations resulting from a high-fat diet combined with PFAS exposure on prostate tumor progression. We evaluated in vivo prostate cancer xenograft models exposed to perfluorooctane sulfonate (PFOS), a type of PFAS compound, and different diets to study the effects of PFAS on prostate cancer progression and metabolic activity. Metabolomics and transcriptomics were used to understand the metabolic landscape shifts upon PFAS exposure. We evaluated metabolic changes in benign or tumor cells that lead to epigenomic reprogramming and altered signaling, which ultimately increase tumorigenic risk and tumor aggressiveness. Our studies are the first in the field to provide new and clinically relevant insights regarding novel metabolic and epigenetic states as well as to support the future development of effective preventative and therapeutic strategies for PFAS-induced prostate cancers. Our findings enhance understanding of how PFAS synergize with high-fat diets to contribute to prostate cancer development and establish an important basis to mitigate PFAS exposure.

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Psoriasis and Cardiovascular Risk—Do Promising New Biomarkers Have Clinical Impact?

Mediators of Inflammation ◽

10.1155/2017/7279818 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Sirje Kaur ◽

Külli Kingo ◽

Mihkel Zilmer

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Epidemiological Studies ◽

Overweight And Obesity ◽

Biologically Active ◽

Cvd Risk ◽

Low Hdl ◽

New Biomarkers ◽

The Impact

Epidemiological studies suggest an increased prevalence of cardiovascular disease (CVD) in patients with psoriasis (PS). Therefore, emphasis has lately been laid on the necessity for clinical evaluation of the risk of CVD in these patients. The systemic inflammatory markers C-reactive protein (CRP) and interleukin- (IL-) 6, which have long been used to predict future CVD in the general population, are increased manyfold in patients with PS. Lipid abnormalities characterized by elevated triglycerides, low HDL cholesterol, and higher concentrations of LDL cholesterol and its oxidized form are also prevalent in patients. There is a need for additional laboratory markers for the assessment of cardiovascular status of patients with PS. Due to frequent comorbid overweight and obesity, biologically active compounds produced by adipocytes may have an impact on monitoring the status of the cardiovascular system of patients with PS. For this purpose, two adipokines, adiponectin and leptin, have been most extensively studied. The review focuses on some inflammatory and oxidative stress aspects in patients with PS through the analysis of the impact of prominent adipokines and oxidized low-density lipoprotein (oxLDL) to assess their eligibility for clinical practice as markers of CVD risk in patients with PS.

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Parental obesity programs pancreatic cancer development in offspring

Endocrine Related Cancer ◽

10.1530/erc-19-0016 ◽

2019 ◽

Vol 26 (5) ◽

pp. 511-523 ◽

Cited By ~ 5

Author(s):

Raquel Santana da Cruz ◽

Johan Clarke ◽

Ana Cristina P Curi ◽

Aseel Al-Yawar ◽

Lu Jin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Body Weight ◽

Control Diet ◽

Epidemiological Studies ◽

Cancer Development ◽

Separate Experiment ◽

Metabolic Dysfunction ◽

History Of ◽

History Of Obesity ◽

The Impact

Epidemiological studies suggest that timing of obesity onset – and underlying metabolic dysfunction – is important in determining pancreatic cancer rates: early and young adult abdominal overweight/obesity is more strongly associated with this cancer than obesity that develops later in life. Parental obesity and overweight are associated with metabolic dysfunction and obesity in their children. Here, we evaluated the impact of parental overweight on offspring’s susceptibility of pancreatic cancer using the P48Cre/+/KrasG12D/+ mouse model. Male mice were fed an obesity-inducing diet (OID) before conception and mated with females raised on a control diet (CO) to generate the offspring. In a separate experiment, pregnant dams were fed CO or OID throughout gestation. The resulting OID offspring from the maternal (OID-m) or paternal lineage (OID-p) were used to study body weight, metabolic parameters and pancreatic cancer development and for molecular analysis. Parental obesity increased offspring’s body weight at birth, weaning and in adulthood compared to CO, with gender- and genotype-specific differences. OID-p and OID-m offspring showed metabolic disorder and accelerated development of high-grade PanIN/PDAC. OID offspring also had higher rates of acinar-to-ductal reprogramming assessed by CPA1+/SOX9+-positive pancreatic cells. Levels of Tenascin C (TNC), an ECM glycoprotein shown to suppress apoptosis, were elevated in OID offspring, particularly females. In line with that, OID offspring displayed increased collagen content and decreased apoptosis in pancreatic lesions compared to CO. An ancestral history of obesity through either the paternal or maternal lineages increases offspring’s susceptibility to pancreatic cancer development.

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Paternal exposure to the pesticide DDT induces intergenerational programming of breast cancer predisposition via sperm miRNA

10.1101/2020.03.23.004135 ◽

2020 ◽

Cited By ~ 1

Author(s):

Raquel Santana da Cruz ◽

Hong Cao ◽

Camile C. Fontelles ◽

Apsra Nasir ◽

Alexandra Krebs ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Disrupting Chemicals ◽

Mammary Tumorigenesis ◽

Epigenetic Inheritance ◽

Epidemiological Studies ◽

Cancer Development ◽

Paternal Exposure ◽

Breast Cancer Development ◽

Breast Cancer Predisposition ◽

The Impact

AbstractBackgroundDNA sequence accounts for the majority of disease heritability, including cancer. However, it is becoming clear that environmentally-induced epigenetic inheritance can also occur. Epidemiological studies have shown that maternal exposure to the pesticide DDT in pregnancy is associated with increased breast cancer risk in women. Yet, the effects of paternal exposure to this and other pesticides on the progeny’s breast cancer development has not been investigated.MethodsMale mice (c57bl/6) were exposed to DDT or to a control-vehicle (CO) solution and used for sperm collection or mating with unexposed females to produce the DDT or CO daughters. In another experiment, normal mouse embryos (zygote stage) were injected with miRNA-10b and implanted into surrogate mothers to produce miR-10b offspring. DDT daughters or miRNA-10b females were used to study breast cancer development and metabolic parameters. Paternal sperm was used for RNA-seq analysis and miRNA expression levels.ResultsPre-conception paternal DDT exposure altered the sperm small non-coding RNA load, with an increase in miRNAs and a specific surge in miRNA-10b levels. DDT offspring weighed less at birth and at weaning, but became overweight and showed metabolic dysfunction in adulthood compared to CO. DDT daughters also showed increased mammary tumorigenesis, developing more aggressive tumors that grew faster than in CO. This tumor phenotype was linked to suppression of the AMPK energy sensing pathway and mTOR activation in mammary tissues. Remarkably, embryonic injection of miRNA-10b recapitulated the mammary gland and tumor phenotypes observed in DDT daughters.ConclusionsTo our knowledge, this is the first report of an association between paternal DDT exposure and breast cancer in offspring. Paternal DDT-induced programming of breast cancer development in daughters is mechanistically linked to sperm miRNA-10b. The impact of DDT and other endocrine disrupting chemicals on sperm and programming of breast and other cancers in offspring needs to be evaluated in humans.

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