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Do Childhood Adverse Events Contribute to Childhood Obesity?

To anyone involved in adult obesity management, harrowing stories of adverse life events that may have significantly contributed to weight gain, are neither uncommon nor surprising.  While retrospective data in adults often implicates adverse events during childhood, longitudinal studies on the role of such events on body weight during childhood are less common.  This is now the topic of a study by Miriam Schiff and colleagues published in Public Health Nutrition. The researchers looked at the relationship between adverse childhood events (ACEs) and excess weight  in longitudinal data from three waves of the second cohort of the US National Survey of Child and Adolescent Well-Being (NSCAW II), which sampled cases from US Child Protective Services investigations that were closed between February 2008 and April 2009 nationwide. The sample included 3170 kids ranging in age between infancy and 14 at baseline.  Abusive and neglectful events were measured using the Conflict Tactics Scale – Parent-Child version at each wave, whereby hitting with a fist or kicking, beating, choking, burning and threatening with or using a knife or gun were coded as physical abuse; leaving a child alone when an adult should be present, not being able to provide food, being too drunk or high, or not being able to get to a doctor when a child needed it were coded as neglect; any forced sexual contact was coded as sexual abuse; so caught up with problems that parent did not tell child (s)he were not loved were coded as emotional neglect and shout/yell/scream, swear or curse, called dumb or lazy or threaten to send away were coded as psychological abuse.  While supporting the hypothesis that ACEs play a role in the development of childhood obesity, both the number and nature of events as well as the sex of the child appear to matter.  Thus, for e.g., while for all youth, neglect as a single event was associated with about 2.5 greater odds of obesity, for girls who experienced neglect, the odds ratio was closer to 5.   Not all ACEs were positively associated with obesity. Thus, girls, experiencing physical abuse or having a parent with mental health problems had decreased odds of obesity (OR = 0.4), while boys who experienced sexual abuse were likewise less likely to develop obesity (OR =0.06). As the authors point out, several limitations to these data must be considered. For one, the assessment of ACEs was entirely based… Read More »

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Why Do People Lose Weight After Metabolic Surgery?

Back in the days, the answer to how bariatric surgery works was rather simple. Mechanistically, you either caused surgical restriction (e.g. vertical banded gastroplasty, adjustable gastric banding) or malabsorption (e.g. jejuno-ileostomy, bilio-pancreatic diversion).  In the meantime, we know that neither restriction nor malabsorption play a significant role (if any) in why bariatric surgery works.  Rather, we now believe that the remarkable long-term success of these surgical interventions is based on important metabolic changes induced by these procedures, thus prompting the renaming of bariatric to metabolic surgery. But what exactly are the metabolic changes induced by the various current procedures, and how do they contribute to the weight loss and other metabolic changes seen in these patients?  This is now the topic of an extensive review by Alina Akalestou and colleagues, published in Endocrine Reviews.  In this paper, the authors discuss what is known about the roles of alterations in the neuroendocrine mechanisms of central appetite control (both wanting and liking), release of gut peptides that change hunger and satiety, as well as change in microbiota and bile acids.  In addition they briefly review the possibility that metabolic surgery impairs adaptive thermogenesis thereby resulting in a greater metabolic rate than to be expected given the magnitude of weight loss.  Overall, the mechanisms are clearly manifold and complex and may vary substantially based on the actual surgical procedure but also on the time course following surgery.  Clearly better understanding these mechanisms should not only inform surgical innovations but also help identify potential pharmacological targets for novel anti-obesity medications.  @DrSharmaBerlin, D

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How Does Energy Expenditure Change Over Time?

One of the often repeated wisdoms regarding changes in energy expenditure as we age, is that we lose about 10-15 Cal per year. According to this formula, someone going from age 20 to age 50 would lose about 300-450 Cal in energy requirements.  But how accurate is this figure and does it really hold true? This is the topic of perhaps the most comprehensive analysis of human energy expenditure over the lifespan ever to be conducted, by Herman Pontzer and colleagues, published in SCIENCE. The researchers investigated the effects of age, body composition, and sex on total expenditure using a large (n= 6421 subjects; 64% female), diverse (n = 29 countries) database of doubly labeled water measurements for subjects aged 8 days to 95 years. In addition they looked at published measures of basal expenditure in neonates and doubly labeled water–measured total expenditure in pregnant and postpartum women.  After adjusting for body size to isolate potential effects of age, sex, and other factors, they found four distinct phases of human energy expenditure.  The first phase applied to neonates, up to 1 year of age. While during their first month neonates had a size-adjusted energy expenditures similar to that of adults, this increased rapidly in the first year so that between 9 and 15 months of age, adjusted total and basal expenditures were nearly ~50% elevated compared with that of adults. The second phase applied to juveniles, 1 to 20 years of age. While total and basal expenditure continued to increase with age throughout childhood and adolescence along with fat-free mass, size-adjusted expenditures steadily declined at a rate of about 3% per year till about age 20, after which it plateaued at adult levels. In contrast to what one might expect, there was no indication of a pubertal increases in adjusted total or basal expenditure. Although men tended to have a higher energy expenditure, the rate of decline was the same for men and women.  Over the third phase, from 20 to 60 years of age, total and basal expenditure and fat-free mass remained stable from ages 20 to 60 years in both sexes. During pregnancy, adjusted total and basal expenditures remained stable with the elevation in unadjusted expenditures matching those expected from the gain in mothers’ fat-free mass and fat mass. Finally, during the fourth phase, starting at about age 60, total and basal expenditure declined at a rate that exceeded… Read More »

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Do Genes Predict Weight Loss After Metabolic Surgery?

Body weight is a highly heritable trait and a host of genes have now been identified as playing a role in its regulation. Furthermore, there is evidence that changes in body weight in response to caloric restriction may also be in part determined by genetic factors.  This naturally leads to the question whether or not weight loss after metabolic surgery may be predicted by genetic screening.  This is the topic of a recent systematic review by Sapana Gupta and colleagues, published in Obesity Surgery. In their analyses of fifty-seven studies that looked at single genes or genetic risk scores in relationship to weight loss after metabolic surgery, they found some (albeit weak) evidence that certain genetic variants (e.g. UCP, FTO, MC4-R) may predict greater or lesser weight loss. However, results were inconsistent and, where stated, of rather modest magnitude (1.5-4.5 kg). Given the host of factors that can potentially influence post-surgical weight loss, this should not be surprising. It is indeed extremely unlikely that a genetic score is likely to reliably predict weight loss in a given individual with sufficient sensitivity and specificity to meaningfully guide clinical decision making.  For this, one would need to not only link genetic markers to weight loss but also to the overall potential clinical benefit including prediction of hard outcomes.  Thus, the clinical utility of a genetic score that predicts a higher probability of a given patient perhaps achieving a 2 kg less weight loss than the average, is rather limited.  At this time, I do not see any value of adding genetic screening to assessing patients’ suitability for metabolic surgery.  @DrSharma,Berlin, D

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Do Gut Hormones Play a Role in Obesity Related Cancers?

Obesity is now well recognised as an important risk factor for cancers of the GI tract including oesophagus, stomach, colon, gall-bladder, liver, and pancreas. Furthermore, weight-loss interventions, particularly bariatric surgery, have been shown to reduce cancer morbidity and mortality in people living with obesity. Traditionally, obesity related cancer risk has been attributed partly to dietary patterns associated with obesity, as well as insulin resistance (with hyperinsulinemia), increased production of pro-inflammatory cytokines, and changes in sex hormones.  Now, a review paper by Maria Angela Guzzardi and colleagues, published in the International Journal of Obesity, discusses the possibility that obesity related alterations in gut hormones may play a hitherto unrecognised role in the etiology of these cancers.  Gut hormones play a vital role in a wide range of processes ranging from local influences on GI motility, exocrine function and the bacteriome to systemic influences on appetite, glucose homeostasis, and immune response.  As an example, the authors discuss the role of GLP-1: “Recent studies have shown that GLP-1 receptor (GLP-1R) agonists might have a beneficial anti-inflammatory role independent from the glycemic regulatory actions. In fact, GLP-1R agonists modulate enteric immune response by activating intestinal intraepithelial lymphocytes GLP1R, which may influence microbiota composition and intestinal inflammation. Therefore, the blunted GLP-1 secretion in obesity contributes to the obesity-related pro-inflammatory condition.” Similarly, vasoactive intestinal peptide (VIP), “…is a regulator of both innate and adaptive immunity, with an anti-inflammatory role. In fact, in innate immune cells, VIP can inhibit the production of pro-inflammatory factors (e.g., TNF-alpha, IL-6, IL1beta, IL12, iNOS) and promote the production of anti-inflammatory factors (e.g., IL-10 and TGF-beta). In the adaptive immune system, VIP shifts the Th1/Th2 balance during CD4 T cell differentiation in favor of Th2 cells, both in vitro and in vivo, primarily through the vasoactive intestinal peptide receptor-2 (VPAC2).” Based on the observation that neoplastic samples have been shown to express receptors for many gut hormones, the authors also discuss at length the evidence that gut hormones could modulate the proliferation and perhaps invasiveness of a wide range of cancers.  However, they also note that, “Overall, existing data are controversial, which might be due to differences between local and systemic effects of the hormone, and among cancer types.” Hopefully this review will prompt further studies exploring the potential role of obesity-related alteration of gut hormones in the pathogenesis of specific tumors, which will open the perspective of new strategies in the… Read More »

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What is it Like to Live with Obesity?

Although I have spent the last 25 years helping patients manage their obesity, I have never had obesity myself (at least not based on BMI). Everything I know about what it must be like living with this chronic disease, I have learnt from what my patients have told me.  Obviously, this is a biased sample, as I have mainly seen patients with more severe obesity and those fortunate enough to have access to an obesity clinic.  So, what is it really like to live with obesity? This is the topic of a systematic review by Emma Farrell and colleagues published in Obesity Reviews. The study included findings from 32 peer-reviewed studies relating to the lived experience of patients with obesity.  Overall, fiive “third-order constructs” or themes emerged from their ethnographic analysis related to 1) the development of obesity, 2) a life limited, 3) stigma, judgment, shame, and blame, 4) treatment and 4) experiences of specific or minority groups.  Interestingly, the researchers actually involved people living with obesity to inform and validate their synthesis. Thus, once the third-order constructs had been identified and described, the researchers met with the study’s Patient Advisory Board (PAB) to discuss the findings and to provide a “phenomenological nod” if advisory board members could relate to the synthesis, recognizing it as an experience that they have or could have had. With regard to the development of obesity, people living with obesity had a wide range of individual experiences to share. While some reported having been heavy since earliest memory, others reported a steady progression, often in response to a major life event. Other reported contributors ranged from negative emotional states and adverse life experiences to genetic predisposition, social pressures, physical environments and sometimes medications. Virtually all experienced weight cycling, often attributable to dieting.  Obesity clearly was a major limiting factor in many people’s lives, leading to social disconnection as well as restrictions in movement, activities, and opportunities. Many participants described a sense of having to put life on hold. Complications of obesity such as diabetes, high blood pressure, and musculoskeletal pain curtailed many participant’s ability to be active and participate in aspects daily life. Judgment, by self and others, was identified as a major contributor to social isolation and the life-limiting effects of obesity. Indeed, experiencing stigma, judgment, shame, and blame was one of the most pervasive and consistent themes to emerge from the analyses. Thus,… Read More »

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