Alimentary TractLeptin Is a Growth Factor for Colonic Epithelial Cells
Abstract
Obesity increases the risk of colon cancer, whereas physical activity reduces the risk. Plasma levels of leptin increase in proportion to the level of obesity and are reduced by physical activity. Leptin acts as a growth factor for several cell types and thus may provide a biological explanation for the observed epidemiological risk factors. The aim of this study was to investigate whether leptin is a growth factor for colonic epithelial cells. The presence of the leptin receptor in human colon cancer cell lines was assessed using reverse-transcription polymerase chain reaction and immunoblotting, and its presence in human colonic tissue was assessed by immunohistochemistry. The effects of leptin in vitro on HT29 cells were assessed by assessing p42/44 mitogen-activated protein kinase phosphorylation, thymidine incorporation, and cell numbers and in vivo in C57BL/6 mice by colonic bromodeoxyuridine incorporation. The leptin receptor is expressed in human colon cancer cell lines and human colonic tissue. Stimulation with leptin leads to phosphorylation of p42/44 mitogen-activated protein kinase and increases proliferation in vitro and in vivo. Leptin is a growth factor in colonic epithelial cells and one that may provide a biological explanation for the observed associations between obesity, physical activity, and colon cancer.
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Obesity and renal cell carcinoma: Biological mechanisms and perspectives
2023, Seminars in Cancer BiologyObesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential “obesity paradox.” Clinically, there is uncertainty whether improved outcomes observed after diagnosis are driven by stage, type of treatment received, or artifacts of longitudinal changes in weight and body composition. The biological mechanisms underlying obesity’s influence on RCC are not fully established, but multiomic and mechanistic studies suggest an impact on tumor metabolism, particularly fatty acid metabolism, angiogenesis, and peritumoral inflammation, which are known to be key biological hallmarks of clear cell RCC. Conversely, high-intensity exercise associated with increased muscle mass may be a risk factor for renal medullary carcinoma, a rare RCC subtype that predominantly occurs in individuals with sickle hemoglobinopathies. Herein, we highlight methodologic challenges associated with studying the influence of obesity on RCC and review the clinical evidence and potential underlying mechanisms associating RCC with BMI and body composition.
The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response
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Obesity and breast cancer
2022, The Link Between Obesity and CancerThere has been an unprecedented increase in the obesity prevalence over the past few decades which has resulted in a profound increase in the number of pathological conditions in women including various types of cancers. Although the association between obesity and developing conditions such as type 2 diabetes, coronary artery disease, stroke, and hypertension has been well examined in the literature, the impact of obesity on cancer incidence, mortality, and morbidity is still being investigated. Obesity is correlated with a higher risk of developing breast cancer in pre-menopausal and post-menopausal women and with worse disease outcomes in women of all ages. The first part of this chapter looks at the epidemiology and risk factors of developing breast cancer. The second part of this chapter examines currently hypothesized molecular mechanisms that may explain the effects of obesity on driving and altering the local immune environment through adipokines and pro-inflammatory mediators to stimulate angiogenesis, tumorigenesis, and the metastatic spread of breast cancer cells. Lastly, the chapter concludes with a discussion of the recent research examining the link between the human host microbiome and the development of breast cancer.
Association of circulating leptin and adiponectin levels with colorectal cancer risk: A systematic review and meta-analysis of case-control studies
2021, Cancer EpidemiologyLeptin and adiponectin are adipokines which have been commonly implicated in carcinogenesis. As such, many studies have investigated the association of circulating leptin and adiponectin levels with colorectal cancer (CRC) risk. However, the results remained inconsistent.
In this work, we performed a systematic review and meta-analysis to precisely examine the association between circulating levels of leptin and adiponectin and CRC risk. A systematic literature search was performed in PubMed/MEDLINE, Scopus, Web of Science, and EMBASE databases from inception until October 2020. The pooled effect size was then estimated by calculating the odds ratio (OR).
A total of 23 records (comprising 26 studies) were included in the meta-analysis. The overall analysis found that circulating levels of leptin and adiponectin were not significantly associated with CRC risk (P > 0.05). Interestingly, subgroup analysis revealed that a higher level of adiponectin was significantly associated with an increased CRC risk among overweight individuals (OR = 1.16; 95 % CI: 1.02, 1.32), and a decreased CRC risk among normal weight individuals (OR = 0.76; 95 % CI: 0.62, 0.92). Besides, a higher level of adiponectin was also significantly associated with a decreased risk of CRC in men (OR = 0.76; 95 % CI: 0.59, 0.98).
In conclusion, circulating leptin level was not associated with CRC risk, but that of adiponectin was associated with CRC risk only in specific subgroups.
Soy intake and colorectal cancer risk: Results from a pooled analysis of prospective cohort studies conducted in china and japan
2020, Journal of NutritionSoy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein.
We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan.
Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center–based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y.
No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98).
No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed.