Infant Antibiotic Exposure and Obesity Risk
With all the interest in the role of the gut bacteriome in the development of obesity, it was only a matter of time before someone examined the relationship between antibiotic use and obesity risk. This is exactly what Anita Kozyrskyj and colleagues from the University of Alberta, Edmonton, Canada, explored in a paper now published in the International Journal of Obesity. For their study they linked rovincial healthcare records to clinical and survey data from a Canadian longitudinal birth cohort study, whereby antibiotic exposure during the first year of life was documented from prescription records. Overweight and central adiposity were determined from anthropometric measurements at ages 9 (n=616) and 12 (n=431) years. According to this analysis, infants receiving antibiotics in the first year of life were about twice as likely to be overweight later in childhood compared to those who were unexposed. However, after adjustment for birth weight, breastfeeding, maternal overweight and other potential confounders, this association persisted in boys but not in girls. The reason for this discrepancy is not clear. Although these findings are in line with the notion that early use of antibiotics may predispose to obesity, it is important to not that these type of studies cannot prove causality. It may well be that other non-measured factors could explain this association (e.g. overprotective or lower SES parents may be more likely to use antibiotics in their infants – both factors are independently associated with higher rates of obesity). Nevertheless, given the rather high rates of antibiotic exposure in infants it appears that this may well be a promising area for further research not just in the context of obesity but also for many of the other conditions that are now believed to be influenced by intestinal flora. @DrSharma Edmonton, AB Azad MB, Bridgman SL, Becker AB, & Kozyrskyj AL (2014). Infant antibiotic exposure and the development of childhood overweight and central adiposity. International journal of obesity (2005) PMID: 25012772 .
Is Weight Gain Typical in Atypical Depression?
Depression or major depressive disorder (MDD) is not only one of the most common psychiatric problems, it also comes in many flavours. While melancholic or “typical” depression is characterized by a loss of pleasure in most or all activities (anhedonia), a failure of reactivity to pleasurable stimuli, psychomotor retardation and a strong sense of guilt, “atypical” depression is characterized by mood reactivity (paradoxical anhedonia), excessive sleep or sleepiness (hypersomnia), a sensation of heaviness in limbs, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection. An important further distinction is that “typical” depression is commonly associated with loss of appetite and weight loss, whereas “atypical” depression typically involves increased appetite (comfort eating), often with significant weight gain. Now a study by Aurélie Lasserre and colleagues from Switzerland, published in JAMA Psychiatry, looks at the risk for weight gain in patients with different forms of depression. The prospective population-based cohort study, included 3054 randomly selected residents of the City of Lausanne (mean age, 49.7 years; 53.1% were women) with 5.5 years of follow-up. Depression subtypes according to the DSM-IV, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured diagnostic interviews. As expected, only participants with the “atypical” subtype of MDD at baseline had a higher increase in adiposity and were about 3.75 times more likely to have developed obesity during follow-up than participants without MDD. This association remained robust even after adjustment for a wide range of confounders. Thus, as the authors note, “The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.“ Although we should be wary of those antidepressants that can cause weight gain, an early diagnosis and treatment of atypical depression may well prevent further weight gain and perhaps facilitate weight loss in patients with atypical depression. Clearly, screening for “atypical” depression must be an essential part of obesity assessment and management. @DrSharma Edmonton, AB Lasserre AM, Glaus J, Vandeleur CL, Marques-Vidal P, Vaucher J, Bastardot F, Waeber G, Vollenweider P, & Preisig M (2014). Depression With Atypical Features and Increase in Obesity, Body Mass Index, Waist Circumference, and Fat Mass: A Prospective, Population-Based Study. JAMA psychiatry PMID:… Read More »
Lack of Oxygen Can Trigger Adipose Tissue Inflammation
Lack of oxygen is a well known stressor for any living cell – this is of course also true for fat cells (adipocytes). But lack of oxygen does not just occur when there is a problem with breathing or blood flow. Lack of oxygen (hypoxia) can also occur a the cellular level, when the cellular oxygen demand exceeds supply. According to what may well be considered a “landmark” paper by Lee and colleagues, published in CELL, it appears that increased adipocyte oxygen consumption may be the key trigger of molecular changes that cause local inflammation and systemic insulin resistance commonly associated with obesity. The paper reports on a series of animal studies with diet-induced obesity (through a high-fat diet), demonstrating that with increasing weight gain, adipocyte respiration in the mitochondria becomes “uncoupled” leading to a significant increase in oxygen consumption with relative hypoxia. This uncoupling appears to be mediated through activation of adenine nucleotide translocase 2 (ANT2), an inner mitochondrial membrane protein, by saturated fatty acids. The resulting hypoxia, in turn, activates the transcription factor HIF-1α, setting off a pro-inflammatory response which in turn leads to insulin resistance with an increased risk of diabetes. The researcher also show that blocking either ANT2 or HIF-1α can prevent these events, thereby suggesting new pharmacological targets for alleviating the pro-inflammatory and metabolic consequences of obesity. Obviously, there is always room for caution in extrapolating animal findings to humans, but this paper is likely to spawn a flurry of similar work in human fat cells. As cellular hypoxia is more likely to occur the larger the fat cell, these studies also tie in the previous observations of a positive association between adipocyte cell size and metabolic abnormalities. Certainly a topic we can expect to hear more of in the not too distant future. @DrSharma Edmonton, AB Lee YS, Kim JW, Osborne O, Oh da Y, Sasik R, Schenk S, Chen A, Chung H, Murphy A, Watkins SM, Quehenberger O, Johnson RS, & Olefsky JM (2014). Increased Adipocyte O2 Consumption Triggers HIF-1α, Causing Inflammation and Insulin Resistance in Obesity. Cell, 157 (6), 1339-52 PMID: 24906151
There Has Not Been A Single Success Story in National Obesity Prevention in The Past 33 Years
Just back from the 21st European Congress on Obesity, I missed out on 100s of media interviews I could have done last week as the media were abuzz with the latest obesity statistics from around the world. In what will clearly be considered a “landmark” paper by ~150 authors published in The Lancet, we now have the latest summary of global, regional and national data on obesity. Based on the analyses of almost 1800 surveys, reports, and published studies, the worldwide prevalence of adults with a body-mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 29 6o 37% in men and from 30 to 38% in women. In 2013, 23% of children and adolescents in developed countries were overweight or obese while the same is true for about ~12% of kids in developing countries. Together, this leave about 2.1 billion of the world populations as currently overweight or obese with numbers growing in virtually every region of the world (albeit with a bit of a slow down in developed countries). Thus, the authors conclude that, “Not only is obesity increasing, but no national success stories have been reported in the past 33 years.” Obviously, there are many reasons why we lack success stories. No doubt, one could point to governments that have not tried hard enough, or the food and leisure industry that sustains its overwhelming influence on consumer “choices”, or the continuing “westernization” of global lifestyles. No doubt, many policies have been tried (e.g. fat taxes, menu labelling, school food programs, fitness taxes, BMI report cards as well as more drastic “shame and blame” tactics) but conclusive evidence that any such measures are working to reverse the tide remains elusive. It may well be that the flattening of obesity (but not severe obesity) rates in developed countries may have more to do with the “natural” history of this epidemic, than with any public health measures. On the other hand, perhaps the reason so little progress has been made in preventing obesity is that we are not going after the right targets, namely to change the actual life experiences of overworked, sleep deprived, stress-out families living in a culture of “grabbing a bite” and “working lunches” at one end and the millions living with poor education and food insecurity at the other. No amount of fiddling with menu labelling is about to change that. What… Read More »
Does Calling You Fat Make You Fat?
One of the most troubling aspects of weight-bias and discrimination is that it has strong negative emotional and physical consequences for the individuals, who perceive these negative attitudes. Now a study suggests that simply being labeled “fat” in childhood may be a strong predictor of obesity ten year later. Thus, according to a longitudinal study by Jeffrey Hunger and Janet Tomiyama, published in JAMA Pediatrics, girls who reported being called “fat” at age 10 were about 60% more likely to have a BMI in the obese range at age 19. Kids in this study were considered as “labeled”, if they responded “yes” to the question, whether they had ever been called fat by their father, mother, brothers, sister, best girl friend, boy you like best, any other girl, any other boy, or teacher. Interestingly enough, this finding is not explained by the possibility that the labelled girls were indeed heavier – there was in fact no difference in BMI at age 10 between the kids who responded “yes” and those, who did not. Indeed, the findings remained robust even after correction for various demographic confounders. These findings are concerning, as they suggest that simply being called “fat” as a kid, may put you on a track to weight gain irrespective of whether or not you actually carry excess weight to start with. I am sure many of my readers will relate to these findings and can tell their own stories of how being “labelled” fat may have influenced their weight journeys. @DrSharma Edmonton, AB Hunger JM, & Tomiyama AJ (2014). Weight Labeling and Obesity: A Longitudinal Study of Girls Aged 10 to 19 Years. JAMA pediatrics PMID: 24781349 .
Watch Dr. Sharma in the News!
Listen to Dr. Sharma!
