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Tissue and circulating microRNAs as biomarkers of response to obesity treatment strategies.
Catanzaro, G, Filardi, T, Sabato, C, Vacca, A, Migliaccio, S, Morano, S, Ferretti, E
Journal of endocrinological investigation. 2021;(6):1159-1174
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Abstract
BACKGROUND Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. AIM: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. RESULTS A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. CONCLUSIONS Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity.
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Physiology of Energy Intake in the Weight-Reduced State.
Berthoud, HR, Seeley, RJ, Roberts, SB
Obesity (Silver Spring, Md.). 2021;:S25-S30
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Physiological adaptations to intentional weight loss can facilitate weight regain. This review summarizes emerging findings on hypothalamic and brainstem circuitry in the regulation of body weight and identifies promising areas for research to improve therapeutic interventions for sustainable weight loss. There is good evidence that body weight is actively regulated in a homeostatic fashion similar to other physiological parameters. However, the defended level of body weight is not fixed but rather depends on environmental conditions and genetic background in an allostatic fashion. In an environment with plenty of easily available energy-dense food and low levels of physical activity, prone individuals develop obesity. In a majority of individuals with obesity, body weight is strongly defended through counterregulatory mechanisms, such as hunger and hypometabolism, making weight loss challenging. Among the options for treatment or prevention of obesity, those directly changing the defended body weight would appear to be the most effective ones. There is strong evidence that the mediobasal hypothalamus is a master sensor of the metabolic state and an integrator of effector actions responsible for the defense of adequate body weight. However, other brain areas, such as the brainstem and limbic system, are also increasingly implicated in body weight defense mechanisms and may thus be additional targets for successful therapies.
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Unintentional Weight Loss in Older Adults.
Gaddey, HL, Holder, KK
American family physician. 2021;(1):34-40
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Abstract
Unintentional weight loss in people older than 65 years is associated with increased morbidity and mortality. Nonmalignant diseases are more common causes of unintentional weight loss in this population than malignant causes. However, malignancy accounts for up to one-third of cases of unintentional weight loss. Medication use and polypharmacy can interfere with the sense of taste or induce nausea and should not be overlooked as causative factors. Social factors such as isolation and financial constraints may contribute to unintentional weight loss. A readily identifiable cause is not found for 6% to 28% of cases. Recommended tests include age-appropriate cancer screenings, complete blood count, basic metabolic panel, liver function tests, thyroid function tests, C-reactive protein level, erythrocyte sedimentation rate, lactate dehydrogenase measurement, ferritin, protein electrophoresis, and urinalysis. Chest radiography and fecal occult blood testing should be performed. Further imaging and invasive testing may be considered based on initial evaluation. When the initial evaluation is unremarkable, a three- to six-month observation period is recommended with follow-up based on clinician and patient preferences. Treatment should focus on the underlying cause if known. Dietary modifications that consider patient preferences and chewing or swallowing disabilities should be considered. Appetite stimulants and high-calorie supplements are not recommended. Treatment should focus on feeding assistance, addressing contributing medications, providing appealing foods, and social support.
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Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?
Papamargaritis, D, le Roux, CW
Nutrients. 2021;(3)
Abstract
Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy-the two most commonly performed bariatric procedures-and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9-39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.
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Why We Eat Too Much, Have an Easier Time Gaining Than Losing Weight, and Expend Too Little Energy: Suggestions for Counteracting or Mitigating These Problems.
Borer, KT
Nutrients. 2021;(11)
Abstract
The intent of this review is to survey physiological, psychological, and societal obstacles to the control of eating and body weight maintenance and offer some evidence-based solutions. Physiological obstacles are genetic and therefore not amenable to direct abatement. They include an absence of feedback control against gaining weight; a non-homeostatic relationship between motivations to be physically active and weight gain; dependence of hunger and satiation on the volume of food ingested by mouth and processed by the gastrointestinal tract and not on circulating metabolites and putative hunger or satiation hormones. Further, stomach size increases from overeating and binging, and there is difficulty in maintaining weight reductions due to a decline in resting metabolism, increased hunger, and enhanced efficiency of energy storage. Finally, we bear the evolutionary burden of extraordinary human capacity to store body fat. Of the psychological barriers, human craving for palatable food, tendency to overeat in company of others, and gullibility to overeat when offered large portions, can be overcome consciously. The tendency to eat an unnecessary number of meals during the wakeful period can be mitigated by time-restricted feeding to a 6-10 hour period. Social barriers of replacing individual physical work by labor-saving appliances, designing built environments more suitable for car than active transportation; government food macronutrient advice that increases insulin resistance; overabundance of inexpensive food; and profit-driven efforts by the food industry to market energy-dense and nutritionally compromised food are best overcome by informed individual macronutrient choices and appropriate timing of exercise with respect to meals, both of which can decrease insulin resistance. The best defense against overeating, weight gain, and inactivity is the understanding of factors eliciting them and of strategies that can avoid and mitigate them.
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The Merits and the Pitfalls of Low Carbohydrate Diet: A Concise Review.
Mooradian, AD
The journal of nutrition, health & aging. 2020;(7):805-808
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Low carbohydrate diets (LCD) may help body weight loss and glycemic control in diabetes but their long-term consequences are not known. The aim of this review is to highlight the contrast between the potential benefits of short term LCD and the adverse health effects of long-term consumption of LCD. LCD can enhance weight loss in the short term although its effect is small and not sustainable. In people with diabetes and insulin resistance, LCD is helpful in achieving glycemic control. However, there are untoward side effects especially when carbohydrates are severely restricted (< 50 gm a day) to induce ketosis. The latter curbs appetite but also may cause nausea, fatigue water and electrolyte losses and limits exercise capacity. In addition, observational studies suggest that low carbohydrate diets (< 40% energy form carbohydrates) as well as very high carbohydrate diets (> 70% energy from carbohydrate) are associated with increased mortality. The available scientific evidence supports the current dietary recommendations to replace highly processed carbohydrates with unprocessed carbohydrates as well as limiting added sugars in the diet.
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Intermittent Fasting and Metabolic Health: From Religious Fast to Time-Restricted Feeding.
Hoddy, KK, Marlatt, KL, Çetinkaya, H, Ravussin, E
Obesity (Silver Spring, Md.). 2020;(Suppl 1):S29-S37
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Over the past 10 to 15 years, intermittent fasting has emerged as an unconventional approach to reduce body weight and improve metabolic health beyond simple calorie restriction. In this review, we summarize findings related to Ramadan and Sunnah fasting. We then discuss the role of caloric restriction not only as an intervention for weight control, but importantly, as a strategy for healthy aging and longevity. Finally, we review the four most common intermittent fasting (IF) strategies used to date for weight management and to improve cardiometabolic health. Weight loss is common after IF but does not appear to be different than daily caloric restriction when compared directly. IF may also provide additional cardiometabolic benefit, such as insulin sensitization, that is independent from weight loss. While no specific fasting regimen stands out as superior at this time, there is indeed heterogeneity in responses to these different IF diets. This suggests that one dietary regimen may not be ideally suited for every individual. Future studies should consider strategies for tailoring dietary prescriptions, including IF, based on advanced phenotyping and genotyping prior to diet initiation.
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The immune remodel: Weight loss-mediated inflammatory changes to obesity.
Phillips, CL, Grayson, BE
Experimental biology and medicine (Maywood, N.J.). 2020;(2):109-121
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Abstract
UNLABELLED Obesity is an escalating world problem that contributes to the complexity and cost of treatment of metabolic disorders. Obesity is the result of increased storage of energy in the form of adipose tissue, reducing the quality of daily life, and interfering with longevity. Obesity is also a chronic, low-grade inflammatory disorder. The inflammatory processes affect many organ systems with expanded numbers of immune cells and increased cytokine production. Long-term weight loss is difficult to achieve and maintain. Lifestyle modifications, pharmacologic treatments, and surgical methods are increasingly utilized to ameliorate excess body weight and the comorbidities of obesity, such as diabetes, cardiovascular disease, dyslipidemia, and cancers. Weight loss is also touted to reduce inflammation. Here we review the current literature on human obesity-related systemic and local changes to the immune system and circulating inflammatory mediators. Further, we consider the impact of weight loss to reduce the burden of inflammation, bearing in mind the different methods of weight loss—behavioral change vs. surgical intervention. IMPACT STATEMENT As the prevalence and severity of obesity expand, the negative impact of excess adiposity affects every system of the body. Given that obesity is a subversive attack on the immune system, weight loss should improve inflammation locally and systemically. Weight management strategies like dieting, exercise, and bariatric surgery, thus have the opportunity to reduce the burden of inflammation.
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The limits and challenges of antiobesity pharmacotherapy.
Gadde, KM, Atkins, KD
Expert opinion on pharmacotherapy. 2020;(11):1319-1328
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INTRODUCTION Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. AREAS COVERED This review covers the history of antiobesity drugs, efficacy, and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization. EXPERT OPINION In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.
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Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review.
Watanabe, M, Risi, R, Masi, D, Caputi, A, Balena, A, Rossini, G, Tuccinardi, D, Mariani, S, Basciani, S, Manfrini, S, et al
Nutrients. 2020;(9)
Abstract
The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.