Growing evidence suggested that Sleep Disorders (SD) could increase the risk of developing obesity and could contribute to worsen obesity-related cardiovascular risk. Further, obesity per se has been reported to blunt sleep homeostasis. This happens through several mechanisms. First of all, the excessive adipose tissue at neck and chest levels could represent a mechanical obstacle to breathe. Moreover, the visceral adipose tissue is known to release cytokines contributing to low-grade chronic inflammation that could impair the circadian rhythm. Also, nutrition plays an important role in sleep homeostasis. High fat and/or high carbohydrate diets are known to have a negative impact on both sleep quality and duration. In addition, obesity predisposes to a condition called "obstructive sleep apnea" that has a detrimental effect on sleep. SD could increase the risk and/or could contribute to worsen cardiovascular risk usually associated with obesity. The chronic low grade inflammation associated with obesity has been reported to increase the risk of developing hypertension, type 2 diabetes and dyslipidemia. In turn, improving quality of sleep has been reported to improve the management of these cardiovascular risk factors. Thus, the aim of this manuscript is to provide evidence on the association of obesity and SD and on how they could contribute to the risk of developing cardiovascular risk factors such as hypertension, dyslipidemia and type 2 diabetes in obesity.
The co-existence of humans and gut microbiota started millions of years ago. Until now, a balance gradually developed between gut bacteria and their hosts. It is now recognized that gut microbiota are key to form adequate immune and metabolic functions and, more in general, for the maintenance of good health. Gut microbiota are established before birth under the influence of maternal nutrition and metabolic status, which can impact the future metabolic risk of the offspring in terms of obesity, diabetes, and cardiometabolic disorders during the lifespan. Obesity and diabetes are prone to disrupt the gut microbiota and alter the gut barrier permeability, leading to metabolic endotoxaemia with its detrimental consequences on health. Specific bacterial sequences are now viewed as peculiar signatures of the metabolic syndrome across life stages in each individual, and are linked to pathogenesis of cardiovascular diseases (CVDs) via metabolic products (metabolites) and immune modulation. These mechanisms have been linked, in association with abnormalities in microbial richness and diversity, to an increased risk of developing arterial hypertension, systemic inflammation, nonalcoholic fatty liver disease, coronary artery disease, chronic kidney disease, and heart failure. Emerging strategies for the manipulation of intestinal microbiota represent a promising therapeutic option for the prevention and treatment of CVD especially in individuals prone to CV events.
Epidemiological data support the view that both obesity and cardiovascular diseases (CVD) account for a high proportion of total morbidity and mortality in adults throughout the world. Obesity and CVD have complex interplay mechanisms of genetic and environmental factors, including diet. Nutrition is an environmental factor and it has a predominant and recognizable role in health management and in the prevention of obesity and obesity-related diseases, including CVD. However, there is a marked variation in CVD in patients with obesity and the same dietary pattern. The different genetic polymorphisms could explain this variation, which leads to the emergence of the concept of nutrigenetics. Nutritional genomics or nutrigenetics is the science that studies and characterizes gene variants associated with differential response to specific nutrients and relating this variation to various diseases, such as CVD related to obesity. Thus, the personalized nutrition recommendations, based on the knowledge of an individual’s genetic background, might improve the outcomes of a specific dietary intervention and represent a new dietary approach to improve health, reducing obesity and CVD. Given these premises, it is intuitive to suppose that the elucidation of diet and gene interactions could support more specific and effective dietary interventions in both obesity and CVD prevention through personalized nutrition based on nutrigenetics. This review aims to briefly summarize the role of the most important genes associated with obesity and CVD and to clarify the knowledge about the relation between nutrition and gene expression and the role of the main nutrition-related genes in obesity and CVD.
Several human and animal studies have demonstrated that cardiometabolic parameters in infancy, childhood, adolescence and even adulthood are negatively influenced by many factors besides energy imbalance. Interestingly, maternal weight excess both before and during pregnancy seems to be a negative determinant of metabolic and cardiovascular outcomes in the offspring. This review includes both human and animal studies and finally highlights the link between maternal obesity and cardiometabolic disorders in offspring.
Waiting for a definite answer from well-designed randomized prospective clinical trials, the impact of the new antiobesity drugs -liraglutide, bupropion/naltrexone, phentermine/topiramate and lorcaserin- on cardiovascular outcomes remains uncertain. What has been learned from previous experience with older medicines is that antiobesity drugs may influence cardiovascular health not only causing weight reduction but also through direct actions on the cardiovascular system. Therefore, in the present review, we examine what is known, mainly from preclinical investigations, about the cardiovascular pharmacology of the new antiobesity medicines with the aim of highlighting potential mechanistic differences. We will show that the two active substances of the bupropion/naltrexone combination both exert beneficial and unwanted cardiovascular effects. Indeed, bupropion exerts anti-inflammatory effects but at the same time it does increase heart rate and blood pressure by potentiating catecholaminergic neurotransmission, whereas naltrexone reduces TLR4-dependent inflammation and has potential protective effects in stroke but also impairs cardiac adaption to ischemia and the beneficial opioid protective effects mediated in the endothelium. On the contrary, with the only exception of a small increase in heat rate, liraglutide only exerts favorable cardiovascular effects by protecting myocardium and brain from ischemic damage, improving heart contractility, lowering blood pressure and reducing atherogenesis. As far as the phentermine/topiramate combination is concerned, no direct cardiovascular beneficial effect is expected for phentermine (as this drug is an amphetamine derivative), whereas topiramate may exert cardioprotective and neuroprotective effects in ischemia and anti-inflammatory and antiatherogenic actions. Finally, lorcaserin, a selective 5HT2C receptor agonist, does not seem to exert significant direct effects on the cardiovascular system though at very high concentrations this drug may also interact with other serotonin receptor subtypes and exert unwanted cardiovascular effects. In conclusion, the final effect of the new antiobesity drugs on cardiovascular outcomes will be a balance between possible (but still unproved) beneficial effects of weight loss and "mixed" weight-independent drug-specific effects. Therefore comparative studies will be required to establish which one of the new medicines is more appropriate in patients with specific cardiovascular diseases.
Cardiovascular diseases (CVD) represent to date the leading cause of mortality in both genders in the developed countries. In this context, a strong need for CVD prevention is emerging through lifestyle modification and nutrition. In fact, several studies linked CVD with unhealthy nutrition, alcohol consumption, stress, and smoking, together with a low level of physical activity. Thus, the primary aim is to prevent and reduce CVD risk factors, such as impaired lipid and glycemic profiles, high blood pressure and obesity. Different types of diet have been, therefore, established to optimize the approach regarding this issue such as the Mediterranean diet, Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. Depending on the diet type, recommendations generally emphasize subjects to increase vegetables, fruits, whole grains, and pulses consumption, but discourage or recommend eliminating red meat, sweets, and sugar-sweetened beverages, along with processed foods that are high in sugar, salt, fat, or low in dietary fiber. In particular, we evaluated and compared the peculiar aspects of these well-known dietary patterns and, thus, this review evaluates the critical factors that increase CVD risk and the potential application and benefits of nutritional protocols to ameliorate dietary and lifestyle patterns for CVD prevention.
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.
Obesity is considered a worldwide epidemic disease. Many pathological conditions have been associated to obesity but the evidence relating to impaired fertility in males with obesity are contrasting. The aim of this review was to evaluate the interplay between obesity and male fertility, analyzing evidence from in vitro and in vivo studies to clinical trials. Obesity seems to be responsible of secondary hypogonadism. Here, we propose a new classification including central, peripheral and testicular factors that may affect the hypothalamic-pituitary-gonadal axis. Moreover, some studies demonstrated a direct action of obesity on sperm count and sperm characteristics, mediated by impaired Sertoli cells function, increased scrotal temperature, oxidative stress and accumulation of toxic substances and liposoluble endocrine disruptors in fat tissue. Recent studies have explored obesity-related epigenetic effects in sperm cells which may cause diseases in offspring. Moreover, not only in females but also males, obesity has been linked to reduced outcomes of in vitro fertilization, with a reduction of pregnancy rate and an increase of pregnancy loss. Finally, we reviewed the effects of weight modifications through diet or bariatric surgery on obesity-related reproductive dysfunction. In this regard, several studies have demonstrated that weight loss has been associated with a restoration of gonadal hormones levels.
Over the past 20 years the use of dietary supplements as adjuvant therapy for weight loss gained growing favor among consumers and dietician–nutritionists, with the subsequent astounding increase in health costs. Despite the reassuring label of natural remedy for losing weight, dietary supplements contain a wide variety of ingredients on which available information is rather scanty and scientifically incomplete. Currently, there is little evidence that weight-loss supplements offer effective aids to reduce weight and meet criteria for recommended use. Robust, randomized, placebo-controlled studies to provide clear-cut scientific evidence of their efficacy and potential side effects in clinical practice are still lacking. Understanding the evidence for the efficacy, safety, and quality of these supplements among nutritionists and physicians is critical to counsel patients appropriately, especially considering the risk of serious adverse effects and interference with concomitant therapies. Detailed information on the efficacy and safety of the most commonly used weight-loss dietary supplements has been recently published by the National Institutes of Health (NIH). However, in this report the thorny issue that may result from drug interactions with weight-loss dietary supplements has been not sufficiently addressed. The aim of this review was to provide a synthetic, evidence-based report on efficacy and safety of the most commonly used ingredients in dietary supplements marketed for weight loss, particularly focusing on their possible drug interactions.
Flavor is the combination of gustatory, olfactory and trigeminal sensations, representing the three main sensory pathways that allow detecting environmental chemical substances. Taste, in particular, is a complex chemosensory path that allows identification of substances present in ingested foods and beverages. In this manuscript, we propose a conceptual roadmap from aspects related to the evolution and the physiological role of taste, up to the current knowledge about its implication in the modulation of a healthy state, or obesity. More specifically, we focused on the role of stimulation of taste receptors in releasing gut hormones (also known as enterohormones), and their effects on the regulation of food intake, by inducing satiety, either by locally acting (in the gastrointestinal tract), or centrally (in the brain). Recent evidence demonstrated that some enterohormones are able to modulate gastrointestinal motility, thus affecting an orexigenic responses in the central nervous system. In keeping with this, we discuss the ability of the gustatory system to be a final checkpoint control for food intake regulation, and we speculate about taste perception manipulation in the management of obesity.
Epidemiological studies reported that vitamin D deficiency represents an increasingly widespread phenomenon in various populations. Vitamin D deficiency is considered a clinical syndrome determined by low circulating levels of 25-hydroxyvitamin D (25(OH)D), which is the biologically-inactive intermediate and represents the predominant circulating form. Different mechanisms have been hypothesized to explain the association between hypovitaminosis D and obesity, including lower dietary intake of vitamin D, lesser skin exposure to sunlight, due to less outdoor physical activity, decreased intestinal absorption, impaired hydroxylation in adipose tissue and 25(OH)D accumulation in fat. However, several studies speculated that vitamin D deficiency itself could cause obesity or prevent weight loss. The fat-solubility of vitamin D leads to the hypothesis that a sequestration process occurs in body fat depots, resulting in a lower bioavailability in the obese state. After investigating the clinical aspects of vitamin D deficiency and the proposed mechanisms for low 25(OH)D in obesity, in this manuscript we discuss the possible role of vitamin D replacement treatment, with different formulations, to restore normal levels in individuals affected by obesity, and evaluate potential positive effects on obesity itself and its metabolic consequences. Food-based prevention strategies for enhancement of vitamin D status and, therefore, lowering skeletal and extra-skeletal diseases risk have been widely proposed in the past decades; however pharmacological supplementation, namely cholecalciferol and calcifediol, is required in the treatment of vitamin D insufficiency and its comorbidities. In individuals affected by obesity, high doses of vitamin D are required to normalize serum vitamin D levels, but the different liposolubility of different supplements should be taken into account. Although the results are inconsistent, some studies reported that vitamin D supplementation may have some beneficial effects in people with obesity.
Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/− bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.
Sponsorship: Publication of this supplement was sponsored by the Association for the Study of Obesity (ASO). All content was reviewed and approved by the ASO Committee, which held full responsibility for the abstract selections.
The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9–39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.
The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors. Unlike dieting, bariatric surgery does a much better job in producing sustained suppression of food intake and body weight, and an intensive search for the underlying mechanisms has started. Although one explanation for this lasting effect of particularly Roux-en-Y gastric bypass surgery (RYGB) is simple physical restriction due to the invasive surgery, a more exciting explanation is that the surgery physiologically reprograms the body weight defense mechanism. In this non-systematic review, we present behavioral evidence from our own and other studies that defended body weight is lowered after RYGB and sleeve gastrectomy. After these surgeries, rodents return to their preferred lower body weight if over- or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis. However, the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute. Future research using both targeted and non-targeted 'omics' techniques in both humans and rodents as well as modern, genetically targeted, neuronal manipulation techniques in rodents will be necessary.
The 17th international symposium in obesity; targeting the gut to treat obesity and its metabolic comorbidities
The microbiota–gut–brain axis is currently being explored in many types of rodent models, including models of behavioral, neurodegenerative and metabolic disorders. Our laboratory is interested in determining the mechanisms and consequences of activation of vagal afferent neurons that lead to activation of parasympathetic reflexes and changes in feeding behavior in the context of obesity. Obesity is associated with microbial dysbiosis, decreased intestinal barrier function, gut inflammation, metabolic endotoxemia, chronic low-grade systemic inflammation and desensitization of vagal afferent nerves. This review will present the evidence that altered gut microbiota together with decreased gut barrier function allows the passage of bacterial components or metabolites in obese individuals, leading to the disruption of vagal afferent signaling and consequently resulting in an increase in body weight. We first review the most recent descriptions of gut microbial dysbiosis due to a high fat diet and describe changes in the gut barrier and the evidence of increased intestinal permeability in obesity. We then will review the evidence to show how manipulating the gut microbiota via pre and probiotics can restore gut barrier function and prevent weight gain. Lastly, we present possible mechanisms by which the microbe–gut–brain axis may have a role in obesity. The studies mentioned in this review have provided new targets to treat and prevent obesity and have highlighted how the microbiota–gut–brain axis is involved.
Gut microbes are now considered as key partners involved in human physiology. Data have shown that microbes contribute to regulate energy, lipid, and glucose homeostasis through several mechanisms. Among them, the role of pathogen-associated molecular pattern and bacterial metabolites has been proposed (for example, metabolic endotoxemia and bioactive lipids). This short review, briefly discusses the role of the gut barrier as well as the impact of both the innate immune system and bioactive molecules (for example, endocannabinoids, cytochrome P450 derived arachidonic acids compounds) in the framework of gut microbes and cardiometabolic disorders.
The neurohumoral signaling systems of the gastrointestinal (GI) tract are considered the most significant of the peripheral inputs controlling both food intake in the short term and energy balance over a longer time course. The importance of the GI tract in the control of energy balance is underscored by the marked beneficial effects of bariatric surgeries for the treatment of obesity. Despite their effectiveness, the mechanisms of bariatric surgery remain to be fully elucidated. Considerable new evidence points to the importance of gut–brain communication, gut barrier function and microbial signaling as three of the most important mechanisms of bariatric surgery-induced weight loss. These mechanisms are reviewed in the present article and the accompanying four papers.
