Obesity and breast cancer in premenopausal women: Current evidence and future perspectives

There is raising evidence reporting an increased incidence of breast cancer over the past decades. Every year approximately 1.4 million new cases of breast cancer are diagnosed worldwide, with a mortality rate of approximately 450,000/year. Out of these cases, 6.6% are diagnosed in premenopausal women with a median age at diagnosis of 40 years: in premenopausal women breast cancer seems to be more aggressive than in post-menopausal women. Obesity has been reported to increase the risk of developing breast cancer and to worsen the prognosis. This seems to be due to several obesity-related mechanisms. Insulin resistance that often occurs with obesity may results in compensatory hyperinsulinemia. Insulin cross-binds insulin-like growth factor-I receptors expressed on breast cells, resulting in proliferative stimuli on breast cancer cells. Besides, hyperinsulinemia up-regulates the growth hormone receptor (GHR) thus increasing GHR stimulation and resulting in an increased hepatic IGF-I synthesis. Moreover, insulin decreases the hepatic expression of binding proteins of IGF-I, such as insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-2, thus leading to high circulating and bioavailable free IGF-I. Additionally, obesity is associated to chronic low-grade inflammation that has been reported to be an additional stimulus for tumor growth. This review shows the current evidence regarding to the association of obesity and breast cancer in premenopausal state focusing on both human and basic studies; showing that the obesity is a risk factor for breast cancer also among premenopausal women, especially for the molecular subtype Triple Negative Breast Cancer

Obesogenic endocrine disruptors and obesity: myths and truths

Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood. Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn. The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences. The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences

Female infertility: which role for obesity?

Obesity is associated with infertility in women through multiple and complex mechanisms. Briefly, the adipose tissue through the production of many factors, such as leptin, free fatty acids (FFA), and cytokines may affect both ovarian and endometrium functions, with a final alteration in oocyte maturation and endometrial epithelium receptivity. In addition, through the development of peripheral insulin resistance obesity produces a condition of functional hyperandrogenism and hyperestrogenism that contribute to produce anovulation and to reduce endometrial receptivity and, therefore participate to cause infertility. Weight loss is able to restore fertility in most cases, but there are no practical indications to guide the clinician to choice the best method among increased physical activity, diet, drugs, and bariatric surgery

Chronotype. what role in the context of gastroenteropancreatic neuroendocrine tumors?

Background Chronotype is defined as a trait determining the subject circadian preference in behavioral and biological rhythms relative to external light-dark cycle. Although individual differences in chronotype have been associated with an increased risk of developing some types of cancer, no studies have been carried out in gastroenteropancreatic neuroendocrine tumors (GEP-NET). Materials We investigate the differences in chronotype between 109 GEP-NET and 109 healthy subjects, gender-, age-, and BMI-matched; and its correlation with tumor aggressiveness. Results GEP-NET patients have a lower chronotype score (p = 0.035) and a higher percentage of evening chronotype (p = 0.003) than controls. GEP-NET patients with morning chronotype had lower BMI, waist circumference, and higher percentage of MetS (p < 0.001) than evening type. Interestingly, considering the clinical pathological characteristics, patients with the presence of metastasis, grading G2, and in progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories. Chronotype score was negatively associated with anthropometric measurements, metabolic profile, percentage of MetS, and Ki67 index (p < 0.001 for all). Conclusions GEP-NET patients have an unhealthy metabolic profile and present more commonly an evening chronotype. These results support the importance of including the assessment of chronotype in an adjunctive tool for the prevention of metabolic alterations and tumor aggressiveness of GEP-NET

Gut: A key player in the pathogenesis of type 2 diabetes?

The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible of the secretion of molecules that may impair insulin secretion/action. At the same time, intestinal milieu regulates the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin, CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism in general and in particular glucose metabolism. Thus, the aim of this paper is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects

Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome

There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21⁻56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD

MORFEO enters final design phase

MORFEO (Multi-conjugate adaptive Optics Relay For ELT Observations, formerly MAORY), the MCAO system for the ELT, will provide diffraction-limited optical quality to the large field camera MICADO. MORFEO has officially passed the Preliminary Design Review and it is entering the final design phase. We present the current status of the project, with a focus on the adaptive optics system aspects and expected milestones during the next project phase

Mediterranean diet and breast cancer risk: a narrative review

Breast cancer is the second most frequent type of cancer worldwide and the most commonly occurring malignancy in women, and its incidence is increasing in most developed and developing countries. There is growing evidence that lifestyle factors, in particular diet may be associated with higher Breast Cancer risk. Some evidence exists regarding the benefit of Mediterranean Diet on reduced risk of Breast Cancer in premenopausal and postmenopausal women. The protective effect of the Mediterranean Diet against the risk of Breast Cancer, is primarily due to principal foods of this nutritional pattern. The principal components of the Mediterranean Diet, such as fruits and vegetables, olive oil, fish and red wine have important antioxidants properties due to their high content of substances like polyphenols, flavonoids, carotenoids and fibers, along with a favourable fatty acid profile, that in turn could reduce the risk of Breast Cancer. Considering the severity of breast cancer and the increasing incidence in the world, there is an increasing interest in promoting prevention strategies in order to reduce the incidence. The aim of this paper is to provide a general overview of the current evidence on the relationship between Breast Cancer and Mediterranean Diet, in premenopausal and postmenopausal women, and to emphasize the potential role of Mediterranean Diet as an effective tool in primary prevention. The possible molecular mechanisms underlying this association will be also pointed out

Influence of the Mediterranean Diet on 25-Hydroxyvitamin D Levels in Adults

The Mediterranean diet (MD) is a dietary pattern effective in terms of prevention of obesity-related diseases, and represents the gold standard in preventive medicine, due to the synergistic action of many nutrients with antioxidant and anti-inflammatory properties. In addition, excess body weight significantly increases the risk of hypovitaminosis D, a well-recognized common feature of individuals with obesity. It is well-known that there is a clear gender difference in the adherence to the MD. The aim of this study was to investigate the association between adherence to the MD and 25-hydroxyvitamin D (25OHD) levels in adults, according to gender. Study population consisted of 617 participants; 296 were males and 321 were females, matched by age and body mass index (BMI). A validated 14-item questionnaire PREDIMED (Prevención con dieta Mediterránea) was used for the assessment of adherence to the MD. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Females have a higher PREDIMED score than males (7.4 ± 2.8 vs. 6.7 ± 3.1 score, p = 0.001), and according to PREDIMED categories, a greater percentage of males had low adherence to the MD compared to their female counterparts (40.2% vs. 37.1%; χ2 = 8.94, p = 0.003). The 25OHD levels were higher in males than in females (18.3 ± 7.3 vs. 16.8 ± 7.8 ng/mL, p = 0.01), and a higher percentage of males had sufficient 25OHD levels (>30 ng/mL) than their female counterparts (10.5% vs. 3.4%, χ2 = 10.96, p < 0.001). Stratifying the sample population according to 25OHD categories, BMI decreased and PREDIMED score increased significantly along with the increased 25OHD levels, in both males and females, respectively (p < 0.001). Looking at the bivariate correlations, PREDIMED score was positively correlated with 25OHD levels after adjusting for age and BMI, in both males (r = 0.21, p < 0.001) and females (r = 0.30, p < 0.001). At the bivariate proportional odds ratio (OR) model, 25OHD levels presented the highest OR values in the category low adherence vs. high adherence to the MD, in both genders (OR 1.21 and OR 1.31, in males and females, respectively). Receiver operator characteristic (ROC) analysis was performed to determine the cut-off values of PREDIMED scores predictive of 25OHD levels: PREDIMED score >5 in males (p < 0.001) and >7 in females (p < 0.001) could serve as thresholds for 25OHD levels above the median. The results of our study highlighted a novel positive association between adherence to the MD and 25OHD levels in both genders. Although 25OHD levels were higher in males than females, 69.7% were deficient. To the best of our knowledge, this is the first study to show that high adherence to the MD is associated with low BMI and high 25OHD levels in both genders, probably through the anti-inflammatory and anti-oxidant effects that are synergistically exerted by either MD or vitamin D on body weight