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1.
Sex and Gender Differences on the Impact of Metabolism-Disrupting Chemicals on Obesity: A Systematic Review.
D'Archivio, M, Coppola, L, Masella, R, Tammaro, A, La Rocca, C
Nutrients. 2024;(2)
Abstract
Obesity represents an important public health concern, being one of the leading causes of death worldwide. It is a multifactorial disease with many underlying intertwined causes, including genetic, environmental and behavioral factors. Notably, metabolism-disrupting chemicals (MDCs) can alter the set point control of metabolism, affecting the development and function of the adipose tissue. Epidemiological studies have reported associations between human exposure to MDCs and several altered metabolic endpoints. It is also noteworthy that sex and gender represent important risk factors in the development of obesity. Different sex-related biological and physiological characteristics influence individual susceptibility, whereas gender represents a critical component in determining the different exposure scenarios. Although some advancements in the treatment of obesity have been achieved in preclinical and clinical studies, the obesity pandemic continues to increase worldwide. The present study performed a systematic review of recent studies considering the effects of MDCs on obesity, with a specific focus on sex- and gender-related responses. This review highlighted that MDCs could differently affect men and women at different stages of life even though the number of studies evaluating the association between obesity and MDC exposure in relation to sex and gender is still limited. This evidence should urge researchers to carry out studies considering sex and gender differences. This is essential for developing sex-/gender-tailored prevention strategies to improve public health policies and reduce exposure.
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2.
Dietary EVOO Polyphenols and Gut Microbiota Interaction: Are There Any Sex/Gender Influences?
D'Archivio, M, Santangelo, C, Silenzi, A, Scazzocchio, B, Varì, R, Masella, R
Antioxidants (Basel, Switzerland). 2022;(9)
Abstract
Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with beneficial health effects and a reduced risk of developing chronic degenerative disorders. The beneficial effects of EVOO can be attributed to its unique composition in monounsaturated fats and phenolic compounds that provide important antioxidant, anti-inflammatory, and immune-modulating activities. On the other hand, it is well known that the gut microbiota has several important roles in normal human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors, among which dietary components play a relevant role. In the last few years, the two-way interaction between polyphenols, including those in EVOO, and the gut microbiota, i.e., the modulation of the microbiota by polyphenols and that of polyphenol metabolism and bioavailability by the microbiota, has attracted growing attention, being potentially relevant to explain the final effects of polyphenols, as well as of the microbiota profile. Furthermore, sex and gender can affect dietary habits, polyphenol intake, and nutrient metabolism. Lastly, it has been recently suggested that differences in gut microbiota composition could be involved in the unequal incidence of metabolic diseases observed between women and men, due to sex-dependent effects on shaping gut microbiota profiles according to diet. This review summarizes the most recent studies on the relationship between EVOO polyphenols and the gut microbiota, taking into account possible influences of sex and gender in modulating such an interaction.
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3.
Obesity-Associated Inflammation: Does Curcumin Exert a Beneficial Role?
Varì, R, Scazzocchio, B, Silenzi, A, Giovannini, C, Masella, R
Nutrients. 2021;(3)
Abstract
Curcumin is a lipophilic polyphenol, isolated from the plant turmeric of Curcuma longa. Curcuma longa has always been used in traditional medicine in Asian countries because it is believed to have numerous health benefits. Nowadays it is widely used as spice component and in emerging nutraceutical food worldwide. Numerous studies have shown that curcumin possesses, among others, potential anti-inflammatory properties. Obesity represents a main risk factor for several chronic diseases, including type 2 diabetes, cardiovascular disease, and some types of cancer. The establishment of a low-grade chronic inflammation, both systemically and locally in adipose tissue, occurring in obesity most likely represents a main factor in the pathogenesis of chronic diseases. The molecular mechanisms responsible for the onset of the obesity-associated inflammation are different from those involved in the classic inflammatory response caused by infections and involves different signaling pathways. The inflammatory process in obese people is triggered by an inadequate intake of nutrients that produces quantitative and qualitative alterations of adipose tissue lipid content, as well as of various molecules that act as endogenous ligands to activate immune cells. In particular, dysfunctional adipocytes secrete inflammatory cytokines and chemokines, the adipocytokines, able to recruit immune cells into adipose tissue, amplifying the inflammatory response also at systemic level. This review summarizes the most recent studies focused at elucidating the molecular targets of curcumin activity responsible for its anti-inflammatory properties in obesity-associated inflammation and related pathologies.
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Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response.
Del Cornò, M, Varì, R, Scazzocchio, B, Varano, B, Masella, R, Conti, L
Cells. 2021;(7)
Abstract
Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.
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5.
Curcuma Longa, the "Golden Spice" to Counteract Neuroinflammaging and Cognitive Decline-What Have We Learned and What Needs to Be Done.
Berry, A, Collacchi, B, Masella, R, Varì, R, Cirulli, F
Nutrients. 2021;(5)
Abstract
Due to the global increase in lifespan, the proportion of people showing cognitive impairment is expected to grow exponentially. As target-specific drugs capable of tackling dementia are lagging behind, the focus of preclinical and clinical research has recently shifted towards natural products. Curcumin, one of the best investigated botanical constituents in the biomedical literature, has been receiving increased interest due to its unique molecular structure, which targets inflammatory and antioxidant pathways. These pathways have been shown to be critical for neurodegenerative disorders such as Alzheimer's disease and more in general for cognitive decline. Despite the substantial preclinical literature on the potential biomedical effects of curcumin, its relatively low bioavailability, poor water solubility and rapid metabolism/excretion have hampered clinical trials, resulting in mixed and inconclusive findings. In this review, we highlight current knowledge on the potential effects of this natural compound on cognition. Furthermore, we focus on new strategies to overcome current limitations in its use and improve its efficacy, with attention also on gender-driven differences.
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6.
Recent Evidence on the Role of Dietary PUFAs in Cancer Development and Prevention.
D'Archivio, M, Scazzocchio, B, Vari, R, Santangelo, C, Giovannini, C, Masella, R
Current medicinal chemistry. 2018;(16):1818-1836
Abstract
BACKGROUND Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. METHODS We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. RESULTS Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. CONCLUSION N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.
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7.
ω3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New Potential Role in Adjuvant Therapies.
Miccadei, S, Masella, R, Mileo, AM, Gessani, S
Frontiers in immunology. 2016;:486
Abstract
Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy. Dietary ω3 polyunsaturated fatty acids (PUFA) have been gaining great interest in recent years as possible anti-inflammatory and anticancer agents, especially in areas such as the large bowel, where the pro-inflammatory context promotes virtually all steps of colon carcinogenesis. Growing epidemiological, experimental, and clinical evidence suggests that ω3 PUFA may play a role in several stages of CRC management exhibiting antineoplastic activity against human CRC cells, improving the efficacy of radiation and chemotherapy, ameliorating cancer-associated secondary complications, and preventing CRC recurrence. These effects are most likely related to the immunomodulatory activities of ω3 PUFA that are able to influence several aspects of the inflammatory process ranging from inflammasome activation, leukocyte recruitment, production of immune mediators to differentiation, and activation of immune cells. In this review, we will focus on the potential use of ω3 PUFA as adjuvant agents together with chemo/radiotherapy, highlighting the immunomodulatory effects most likely responsible for their beneficial effects in different stages of CRC management.
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Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives.
Santangelo, C, Zicari, A, Mandosi, E, Scazzocchio, B, Mari, E, Morano, S, Masella, R
The British journal of nutrition. 2016;115(7):1129-44
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Plain language summary
Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Women with GDM are at a high risk of developing type 2 diabetes (T2D) later in life. Moreover, uncontrolled GDM is linked with a detrimental intra-uterine environment, which leads to foetal complications and an increased risk for the child of developing obesity and metabolic disorders. The aim of the review is to examine the current knowledge and issues about the impact of dietary polyphenols on the mechanisms and/or factors regulating glucose homeostasis, inflammation and adipose tissue function in metabolic alterations linked with GDM. Moreover, this study also reviews the role of Omega-3 fatty acids in pregnancy. The study is a descriptive review based on several studies. Literature data is mainly derived from in vitro and animal models. In vitro and animal studies show that almost all subclasses of flavonoids, stilbene RSV and some olive oil phenolic compounds, interact and modulate several molecular pathways regulating insulin. Obesity worsens GDM with increased risk of developing metabolic disorders in both mother and offspring later in life. The adoption of healthy lifestyle, with adherence to a healthy dietary pattern, has positive effects on the prevention and management of diabetes.
Abstract
Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the 'omics' world, is needed to better understand the complex interaction between dietary compounds and GDM.
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Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin.
Santangelo, C, Filesi, C, Varì, R, Scazzocchio, B, Filardi, T, Fogliano, V, D'Archivio, M, Giovannini, C, Lenzi, A, Morano, S, et al
Journal of endocrinological investigation. 2016;(11):1295-1301
Abstract
AIM: Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). METHODS Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. RESULTS HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). CONCLUSIONS Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.
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Gender-related differences in lifestyle may affect health status.
Varì, R, Scazzocchio, B, D'Amore, A, Giovannini, C, Gessani, S, Masella, R
Annali dell'Istituto superiore di sanita. 2016;(2):158-66
Abstract
Consistent epidemiological and clinical evidence strongly indicates that chronic non-communicable diseases are largely associated with four lifestyle risk factors: inadequate diet, physical inactivity, tobacco use, and excessive alcohol use. Notably, obesity, a worldwide-growing pathological condition determined by the combination between inadequate diet and insufficient physical activity, is now considered a main risk factor for most chronic diseases. Dietary habits and physical activity are strongly influenced by gender attitudes and behaviors that promote different patterns of healthy or unhealthy lifestyles among women and men. Furthermore, different roles and unequal relations between genders strongly interact with differences in social and economic aspects as well as cultural and societal environment. Because of the complex network of factors involved in determining the risk for chronic diseases, it has been promoting a systemic approach that, by integrating sex and gender analysis, explores how sex-specific biological factors and gender-related social factors can interact to influence the health status.