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1.
DNA methylation markers in obesity, metabolic syndrome, and weight loss.
Samblas, M, Milagro, FI, Martínez, A
Epigenetics. 2019;(5):421-444
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Abstract
The fact that not all individuals exposed to the same environmental risk factors develop obesity supports the hypothesis of the existence of underlying genetic and epigenetic elements. There is suggestive evidence that environmental stimuli, such as dietary pattern, particularly during pregnancy and early life, but also in adult life, can induce changes in DNA methylation predisposing to obesity and related comorbidities. In this context, the DNA methylation marks of each individual have emerged not only as a promising tool for the prediction, screening, diagnosis, and prognosis of obesity and metabolic syndrome features, but also for the improvement of weight loss therapies in the context of precision nutrition. The main objectives in this field are to understand the mechanisms involved in transgenerational epigenetic inheritance, and featuring the nutritional and lifestyle factors implicated in the epigenetic modifications. Likewise, DNA methylation modulation caused by diet and environment may be a target for newer therapeutic strategies concerning the prevention and treatment of metabolic diseases.
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Interplay between the Adaptive Immune System and Insulin Resistance in Weight Loss Induced by Bariatric Surgery.
Villarreal-Calderón, JR, Cuéllar, RX, Ramos-González, MR, Rubio-Infante, N, Castillo, EC, Elizondo-Montemayor, L, García-Rivas, G
Oxidative medicine and cellular longevity. 2019;:3940739
Abstract
Low-grade chronic inflammation plays a pivotal role among other pathophysiological mechanisms involved in obesity. Innate and adaptive immune cells undergo systemic proinflammatory polarization that gives rise to an increased secretion of proinflammatory cytokines, which in turn leads to insulin resistance. Bariatric surgery is currently the most effective treatment for obesity, as it brings on significant weight loss, glucose metabolism improvement, and a decrease in systemic inflammation biomarkers. After bariatric surgery, several changes have been reported to occur in adaptive immunity, including reduction in CD4+ and CD8+ T cell counts, a decrease in the Th1/Th2 ratio, an increase in B regulatory cells, and reduction in proinflammatory cytokine secretion. Overall, there seems to be a major shift in several lymphocyte populations from a proinflammatory to an anti-inflammatory phenotype. Furthermore, increased antioxidant activity and reduced lipid and DNA oxidation products have been reported after bariatric surgery in circulating mononuclear cells. This paper highlights the shift in the adaptive immune system in response to weight loss and improved insulin sensitivity, as well as the interplay between immunological and metabolic adaptations as a result of bariatric surgery. Finally, based on data from research, we propose several mechanisms such as changes in adaptive immune cell phenotypes and their by-products, recruitment in adipose tissue, reduced oxidative stress, and modification in metabolic substrate availability as drivers to reduce low-grade chronic inflammation after bariatric surgery in severe obesity.
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Metabolic adaptations during negative energy balance and their potential impact on appetite and food intake.
Casanova, N, Beaulieu, K, Finlayson, G, Hopkins, M
The Proceedings of the Nutrition Society. 2019;(3):279-289
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Abstract
This review examines the metabolic adaptations that occur in response to negative energy balance and their potential putative or functional impact on appetite and food intake. Sustained negative energy balance will result in weight loss, with body composition changes similar for different dietary interventions if total energy and protein intake are equated. During periods of underfeeding, compensatory metabolic and behavioural responses occur that attenuate the prescribed energy deficit. While losses of metabolically active tissue during energy deficit result in reduced energy expenditure, an additional down-regulation in expenditure has been noted that cannot be explained by changes in body tissue (e.g. adaptive thermogenesis). Sustained negative energy balance is also associated with an increase in orexigenic drive and changes in appetite-related peptides during weight loss that may act as cues for increased hunger and food intake. It has also been suggested that losses of fat-free mass (FFM) could also act as an orexigenic signal during weight loss, but more data are needed to support these findings and the signalling pathways linking FFM and energy intake remain unclear. Taken together, these metabolic and behavioural responses to weight loss point to a highly complex and dynamic energy balance system in which perturbations to individual components can cause co-ordinated and inter-related compensatory responses elsewhere. The strength of these compensatory responses is individually subtle, and early identification of this variability may help identify individuals that respond well or poorly to an intervention.
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Weight Loss and Hypertension in Obese Subjects.
Fantin, F, Giani, A, Zoico, E, Rossi, AP, Mazzali, G, Zamboni, M
Nutrients. 2019;(7)
Abstract
Arterial hypertension is strongly related to overweight and obesity. In obese subjects, several mechanisms may lead to hypertension such as insulin and leptin resistance, perivascular adipose tissue dysfunction, renal impairment, renin-angiotensin-aldosterone-system activation and sympathetic nervous system activity. Weight loss (WL) seems to have positive effects on blood pressure (BP). The aim of this review was to explain the mechanisms linking obesity and hypertension and to evaluate the main studies assessing the effect of WL on BP. We analysed studies published in the last 10 years (13 studies either interventional or observational) showing the effect of WL on BP. Different WL strategies were taken into account-diet and lifestyle modification, pharmacological intervention and bariatric surgery. Although a positive effect of WL could be identified in each study, the main difference seems to be the magnitude and the durability of BP reduction over time. Nevertheless, further follow-up data are needed: there is still a lack of evidence about long term effects of WL on hypertension. Hence, given the significant results obtained in several recent studies, weight management should always be pursued in obese patients with hypertension.
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Low-calorie diets in the management of type 2 diabetes mellitus.
Lean, MEJ
Nature reviews. Endocrinology. 2019;(5):251-252
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Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes.
Isaacs, D, Yager, S, Parker, M, Wolfe, L, Luxenburg, J, Lekic, S
The Annals of pharmacotherapy. 2019;(4):371-384
Abstract
OBJECTIVE People with type 1 diabetes often have suboptimal glycemic control. The gold standard of treatment is basal-bolus insulin or subcutaneous insulin infusion via insulin pump. Although insulin therapy improves glycemic control, weight gain and hypoglycemia often limit achievement of hemoglobin A1C (A1C) goals. The number of people with type 1 diabetes who are overweight or obese is increasing, and there are many similarities between what was historically called type 1 and type 2 diabetes. Therefore, there is rationale for using antihyperglycemic agents that target other pathophysiological abnormalities to facilitate weight loss and improve glycemic control. DATA SOURCES We performed a MEDLINE search from 1975 through October 2018 to identify articles that studied noninsulin agents in adults with type 1 diabetes and body mass index (BMI) ≥25 kg/m2. STUDY SELECTION AND DATA EXTRACTION Identified articles were included if the study duration was ≥4 weeks, included ≥20 patients, and set mean baseline BMI ⩾25kg/m2. DATA SYNTHESIS This review summarizes 32 clinical trials. Amylin mimetics, sodium-glucose-like transporter-2 inhibitors, and glucagon-like-peptide-1 receptor agonists demonstrate the greatest improvements in body weight and A1C. The most common adverse effects are hypoglycemia and ketosis. Relevance to Patient Care and Clinical Practice: Patients with type 1 diabetes may have interest in starting noninsulin agents. Clinicians need to be knowledgeable in the efficacy and adverse effect profile of these agents, specifically in people with type 1 diabetes. CONCLUSIONS Adding noninsulin antihyperglycemic agents may benefit select overweight or obese adults with type 1 diabetes. These agents are off-label, and if used, close monitoring is essential.
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A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans.
Sargeant, JA, Henson, J, King, JA, Yates, T, Khunti, K, Davies, MJ
Endocrinology and metabolism (Seoul, Korea). 2019;(3):247-262
Abstract
Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.
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Breastfeeding and postpartum weight loss.
Lambrinou, CP, Karaglani, E, Manios, Y
Current opinion in clinical nutrition and metabolic care. 2019;(6):413-417
Abstract
PURPOSE OF REVIEW Postpartum weight retainment is common in women, increasing the long-term likelihood of overweight and/or obesity. On the other hand, breastfeeding entails a high energy cost that contributes to the total energy expenditure of the mother, increasing the chances of a negative energy equilibrium that could potentially lead to weight loss. This review explores this association as depicted in the latest literature available. RECENT FINDINGS Several studies reported a positive association between breastfeeding and postpartum weight loss while others reported no significant association. Several potential mechanisms, metabolic pathways and determinants have been described. SUMMARY Even though several studies support the potentially beneficial role of breastfeeding in postpartum weight loss, more studies with robust designs are needed to reach a reliable conclusion. Healthcare providers should encourage breastfeeding, not only for its health benefits for both the mother and the offspring but also for its potential role in weight loss.
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A ketogenic diet for reducing obesity and maintaining capacity for physical activity: hype or hope?
Murphy, EA, Jenkins, TJ
Current opinion in clinical nutrition and metabolic care. 2019;(4):314-319
Abstract
PURPOSE OF REVIEW This review will evaluate the recent scientific literature on the efficacy of the ketogenic diet for enhancing weight loss and maintaining capacity for physical activity. RECENT FINDINGS With the increasing obesity epidemic, the 21st century has witnessed the emergence of various diet programs aimed at promoting weight loss and enhancing physical performance. The ketogenic diet, a diet high in fat and low in carbohydrates, has been at the forefront. Recent literature has documented significant weight-loss following ketogenic diet interventions. This has been associated with a decrease in systemic inflammation, reduced insulin resistance, and improved lipid profile. Given the importance of physical activity to sustaining a healthy weight, the impact of a ketogenic diet on physical performance has been investigated. The majority of the current literature supports a positive influence of the ketogenic diet on physical activity owing to its ability to maintain performance of both endurance and resistance activities. We highlight the most important recent advances that have been made on the ketogenic diet in relation to obesity and capacity for physical activity. SUMMARY The ketogenic diet is a potentially promising diet for reducing obesity while maintaining capacity for physical activity. However, questions surrounding the sustainability of this diet for the long-term remain.
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Pancreas Cancer-Associated Weight Loss.
Hendifar, AE, Petzel, MQB, Zimmers, TA, Denlinger, CS, Matrisian, LM, Picozzi, VJ, Rahib, L, ,
The oncologist. 2019;(5):691-701
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Abstract
Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation.