Insights into the Link Between Obesity and Cancer

Ackerman, Sarah E.; Blackburn, Olivia A; Marchildon, François; Cohen, Paul

doi:10.1007/s13679-017-0263-x

Cited by 98 publications

(67 citation statements)

References 102 publications

(88 reference statements)

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“…Until now, the pathophysiological processes for the increased cancer risk in obesity remain unresolved. Besides altered adipokine levels, increased secretion of growth factors and steroid hormones, oxidative stress, an altered microbiome, and low-grade inflammation have been discussed to influence cancer development in obese individuals (15)(16)(17). The excessive fat accumulation promotes a state of a systemic chronic low-grade inflammation, a condition characterized by an increased secretion of pro-inflammatory factors caused by the augmented number of adipocytes and immune cells in adipose tissue (18).…”

Section: Introductionmentioning

confidence: 99%

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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Obesity is accompanied by a systemic chronic low-grade inflammation as well as dysfunctions of several innate and adaptive immune cells. Recent findings emphasize an impaired functionality and phenotype of natural killer (NK) cells under obese conditions. This review provides a detailed overview on research related to overweight and obesity with a particular focus on NK cells. We discuss obesity-associated alterations in subsets, distribution, phenotype, cytotoxicity, cytokine secretion, and signaling cascades of NK cells investigated in vitro as well as in animal and human studies. In addition, we provide recent insights into the effects of physical activity and obesity-associated nutritional factors as well as the reduction of body weight and fat mass on NK cell functions of obese individuals. Finally, we highlight the impact of impaired NK cell physiology on obesity-associated diseases, focusing on the elevated susceptibility for viral infections and increased risk for cancer development and impaired treatment response.NK cells are large granular lymphocytes that mediate rapid innate immunity against viruses, bacteria, parasites, and tumor cells without prior sensitization. NK cells primarily develop and mature in the bone marrow, migrate through the bloodstream, and seed into secondary lymphoid organs, like thymus, spleen, and lymph nodes as well as in other peripheral tissues, like lung, liver, kidney, uterus, and the gastrointestinal tract (23). In blood, NK cells represent 1-6% of all leukocytes and comprise up to 15% of human peripheral blood mononuclear cells (PBMCs). Human NK cells have been defined by the expression of adhesion molecule CD56 and by the absence of the T cell marker CD3. Based on their expression level of CD56 and the Fcγ receptor CD16, NK cells are subdivided into different subpopulations. The two major and classically defined subsets are the CD56 dim CD16 bright NK cells and the CD56 bright CD16 dim/neg NK cells. CD56 dim CD16 bright NK cells represent about 90% of all NK cells and are predominantly found in peripheral blood (24). They are mostly responsible for cytotoxic activity and target cell killing but are also a source of pro-inflammatory Abbreviations: ACM, adipocyte-conditioned media; Adamts3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 3; AdipoR, adiponectin receptor; Anxa8, annexin A8; AT, adipose tissue; Bax, Bcl-2-associated X protein; Bcl, B-cell lymphoma; BMI, body mass index; CCR, CC chemokine receptor; Csf1r, colony stimulating factor 1 receptor; CX3CR1, C-X3-C-motif chemokine receptor 1; DNAM-1, DNAX accessory molecule-1; ESR, estrogen receptor; FasL, Fas ligand; IFN-γ, interferon; GM-CSF; granulocyte macrophage colony-stimulating factor; H6pd, hexose-6-phosphate dehydrogenase; Hk2, hexokinase 2; IL, interleukinIL-6R; interleukin-6 receptor; Il18rap, interleukin 18 receptor accessory protein; IP-10, interferon gamma-induced protein 10; JAK, Janus kinase; KIR, killer immunoglobulin-like receptor; Klra1, killer lectin-like receptor subfamil...

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Section: Introductionmentioning

confidence: 99%

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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“…In a recent review by Ackerman et al., the authors present a summary of the epidemiological evidence that links obesity and cancer as well as several mechanisms for this link, including insulin growth factors, adipokines, cytokines, and leptin. In addition, the authors describe possible therapeutic considerations and some of the unanswered questions that are related to this possible association 11 . Moreover, this association between obesity and cancer is not limited to only one type of cancer but to many, including pancreatic, liver, breast, and female reproductive system cancers 12 …”

Section: Introductionmentioning

confidence: 99%

Pre‐pregnancy obesity and childhood malignancies: A population‐based cohort study

Kessous

Wainstock

2020

Pediatric Blood & Cancer

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Condensation:The association between pre-pregnancy obesity and long-term risk for childhood malignancy. AbstractObjective: Exploring the effect of maternal obesity during pregnancy on the long-term health of offspring is of great importance. The aim of this study was to evaluate the association between maternal pre-pregnancy obesity and future risk of childhood malignancies. Study design:A population-based cohort analysis comparing the risk for long-term childhood malignancies (up to the age of 18 years) in children born to mothers with and without pre-pregnancy obesity (body mass index > 30) was conducted in July 2017. Childhood malignancies were predefined based on ICD-9 codes, as recorded in the hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. The Kaplan-Meier survival curve was constructed to compare cumulative oncological morbidity in both groups over time. The Cox proportional hazards model was used to control for confounders. Results:During the study period, 241 273 infants met the inclusion criteria; 3268 were born to mothers with pre-pregnancy obesity. Children of obese women had significantly increased risk for several childhood malignancies (including brain tumors) as well as increased risk for total hospitalizations with malignancy diagnoses, even after controlling for several confounders (adjusted HR 1.90, 95% CI 1.07-3.37, P = 0.028). Cumulative incidence of oncological morbidity was also significantly increased over time in the studied group (log-rank P = 0.023). Conclusion:Maternal pre-pregnancy obesity is significantly associated with an increased longterm risk for general childhood malignancies, and specifically brain tumors in the offspring. These results are important when counseling mothers regarding potential future risks and recommended lifestyle modifications. K E Y W O R D Sbrain tumor, childhood malignancy, intrauterine environment, pre-pregnancy obesity

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“…In 2016, approximately 39% of the world's adult population were overweight and approximately 13% were obese. Overweight and obesity are defined as the abnormal or excessive accumulation of fat that is closely linked to the development of chronic disorders such as cardiovascular diseases [1], type 2 diabetes [2], musculoskeletal disorders [3] and some cancers [4]. Nevertheless, obesity can be prevented by lifestyle intervention, such as restricting caloric intake and increasing regular physical activity.…”

Section: Introductionmentioning

confidence: 99%

“…The number of each cluster is indicated. The 5ISO structure was used (panels (B), (C), (D), and (E)), and panel B shows the three AMP binding sites(1,2,3), the ATP binding site in the catalytic domain(4), and the regulatory site in the interaction zone between the alpha-2 and beta-1 subunits(5). Finally, panel (A) shows the molecular structures of loganic acid, luteolin-7-diglucuronide, and verbascoside.…”

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confidence: 99%

The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders

et al. 2019

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Lippia citriodora (LC) represents a complex plant-derived source of polyphenols and iridoids that has shown beneficial properties against obesity-related metabolic disorders. The complete extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell and animal models. In this work, we aimed to elucidate the contribution of the different compounds present in the LC extract on the AMPK activation capacity of the whole extract. Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma subunit and/or the different sites of the interaction zones between the gamma and beta subunits. Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside, the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research aimed to develop optimized combinations of polyphenols as a new nutritional strategy against obesity-related metabolic disorders.

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Insights into the Link Between Obesity and Cancer

Cited by 98 publications

References 102 publications

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

Pre‐pregnancy obesity and childhood malignancies: A population‐based cohort study

The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders

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