Obesity and cancer risk: Emerging biological mechanisms and perspectives

Avgerinos, Konstantinos I.; Spyrou, Nikolaos; Mantzoros, Christos S.; Dalamaga, Maria

doi:10.1016/j.metabol.2018.11.001

Cited by 918 publications

(737 citation statements)

References 244 publications

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“…45,46 Although it is known that the development of insulin resistance contributes to the etiology of several human diseases, the phenomenon remains poorly understood at the molecular level. 45,46 Although it is known that the development of insulin resistance contributes to the etiology of several human diseases, the phenomenon remains poorly understood at the molecular level.…”

Section: Discussionmentioning

confidence: 99%

“…Insulin resistance is a major cause of type 2 diabetes and a risk factor for other debilitating health conditions such as cardiovascular disease, cancer, and obesity. 45,46 Although it is known that the development of insulin resistance contributes to the etiology of several human diseases, the phenomenon remains poorly understood at the molecular level. 47,48 This study identifies Gpr27 as a previously unknown player in the development of insulin resistance and presents new opportunities for dissecting the molecular pathways leading to defects in insulin action.…”

Section: Discussionmentioning

confidence: 99%

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Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

Nath

Chen

et al. 2019

FASEB j.

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G protein-coupled receptors (GPCRs) comprise the largest group of membrane receptors in eukaryotic genomes and collectively they regulate nearly all cellular processes.Despite the widely recognized importance of this class of proteins, many GPCRs remain understudied. G protein-coupled receptor 27 (Gpr27) is an orphan GPCR that displays high conservation during vertebrate evolution. Although, GPR27 is known to be expressed in tissues that regulate metabolism including the pancreas, skeletal muscle, and adipose tissue, its functions are poorly characterized. Therefore, to investigate the potential roles of Gpr27 in energy metabolism, we generated a whole body gpr27 knockout zebrafish line. Loss of gpr27 potentiated the elevation in glucose levels induced by pharmacological or nutritional perturbations. We next leveraged a mass spectrometry metabolite profiling platform to identify other potential metabolic functions of Gpr27. Notably, genetic deletion of gpr27 elevated medium-chain acylcarnitines, in particular C6-hexanoylcarnitine, C8-octanoylcarnitine, C9-nonanoylcarnitine, and C10-decanoylcarnitine, lipid species known to be associated with insulin resistance in humans. Concordantly, gpr27 deletion in zebrafish abrogated insulin-dependent Akt phosphorylation and glucose utilization. Finally, loss of gpr27 increased the expression of key enzymes in carnitine shuttle complex, in particular the homolog to the brain-specific isoform of CPT1C which functions as a hypothalamic energy senor. In summary, our findings shed light on the biochemical functions of Gpr27 by illuminating its role in lipid metabolism, insulin signaling, and glucose homeostasis. K E Y W O R D Scarnitine palmitoyltransferase I, G protein-coupled receptors, insulin resistance, lipid metabolism, metabolomic profiling * SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Nath AK, Ma J, Chen Z-Z, et al. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. The FASEB Journal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

Nath

Chen

et al. 2019

FASEB j.

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“…The molecular link between obesity and breast cancer depends on the effects and the interplay between cancer cells and different adipokines, such as adiponectin, leptin, resistin, visfatin, hepatocyte growth factor, TNF‐α, IL‐1, IL‐6, MCP‐1 and other . As mentioned before, the tight interaction between mammary adiposity and breast tissue makes that the adipokines, secreted by mammary fat pad and tumour microenvironment, play a crucial paracrine role in influencing breast cancer progression and metastasis.…”

Section: Functional Interaction Between Adiponectin and Other Adipokinesmentioning

confidence: 98%

Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression

et al. 2020

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Summary This review describes the multifaceted effects of adiponectin on breast cancer cell signalling, tumour metabolism, and microenvironment. It is largely documented that low adiponectin levels are associated with an increased risk of breast cancer. However, it needs to be still clarified what are the extents of the decrease of local/intra‐tumoural adiponectin concentrations, which promote breast tumour malignancy. Most of the anti‐proliferative and pro‐apoptotic effects induced by adiponectin have been obtained in breast cancer cells not expressing estrogen receptor alpha (ERα). Here, we will highlight recent findings demonstrating the mechanistic effects through which adiponectin is able to fuel genomic and non‐genomic estrogen signalling, inhibiting LKB1/AMPK/mTOR/S6K pathway and switching energy balance. Therefore, it emerges that the reduced adiponectin levels in patients with obesity work to sustain tumour growth and progression in ERα‐positive breast cancer cells. All this may contribute to remove the misleading paradigm that adiponectin univocally inhibits breast cancer cell growth and progression independently on ERα status. The latter concept, here clearly provided by pre‐clinical studies, may have translational relevance adopting adiponectin as a potential therapeutic tool. Indeed, the interfering role of ERα on adiponectin action addresses how a separate assessment of adiponectin treatment needs to be considered in novel therapeutic strategies for ERα‐positive and ERα‐negative breast cancer.

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“…Developed countries show the highest rates of adults affected by obesity. While the impact of BMI on diabetes and on heart disease is well known, the relation to breast cancer and other human cancers remain a current topic 21, 22 . Obesity is an important risk factor to breast cancer development and there is a substantial association with postmenopausal women, as well as worse prognosis for women at all ages 21 .…”

Section: Obesitymentioning

confidence: 99%

Risk factors related to breast cancer development

Bastos¹

2019

Mastology

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O câncer de mama é uma doença que acomete mulheres em todo o mundo, sendo por isso um problema de saúde de preocupação global. Apesar dos avanços científicos e tecnológicos nas pesquisas básicas e nos estudos clínicos, o câncer de mama ainda apresenta inúmeras barreiras que necessitam ser transpostas, a fim de garantir melhor sobrevida às pacientes acometidas por essa doença. A atuação da ciência consiste não apenas em prever as melhores formas de tratamento, mas também de como evitar o aparecimento dos sintomas e, por consequência, do tumor. Artigos recentes discutem inúmeros fatores que podem contribuir para a iniciação e progressão tumoral. São considerados os hábitos sociais, como o ato de fumar, ingestão de bebidas alcoólicas, dietas que contribuam para a hiperlipidemia ou aumento da disponibilidade de moléculas antagonistas que agem sobre a célula de modo a construir um microambiente favorável à tumorigênese. Além disso, fatores ligados ao histórico familiar e predisposição hereditária são importantes, apesar de explicar uma parcela mínima dos casos. Com isso, o presente artigo tem por objetivo abordar sobre fatores de risco modificáveis e não modificáveis, relacionados com a progressão do câncer de mama. ABSTRACTBreast cancer is a disease that affects women worldwide, and therefore is a health problem of global concern. Despite scientific and technological advances in basic researches and in clinical studies, breast cancer still presents numerous obstacles that need to be overcome in order to ensure better survival for patients affected by this disease. Science's work is not only to predict the best methods of treatment, but also to prevent the onset of symptoms and, consequently, of the tumor. Recent articles discuss numerous factors which may contribute to tumor initiation and progression. They take into consideration social habits, such as smoking, alcohol drinking, diets that contribute to hyperlipidemia or increased availability of antagonist molecules that act on the cell in order to create a favorable microenvironment to tumorigenesis. In addition to that, factors related to family history and hereditary predisposition are important, even though they explain a minimal portion of cases. Thus, the purpose of this article is to address modifiable and non-modifiable risk factors, related to breast cancer progression.

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Obesity and cancer risk: Emerging biological mechanisms and perspectives

Cited by 918 publications

References 244 publications

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish

Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression

Risk factors related to breast cancer development

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