100+ Putative Causes Of Obesity – Take Your Pick

Listening to (or reading the bestsellers written by) pundits, one may easily think that the entire obesity problem can be brought down to a couple of factors – sugar-sweetened beverages, fast food, sedentariness, screen-time, – take your pick. Now, Morgan Downey, former CEO of the Obesity Society on his blog – the Downey Obesity Report – provides an update of previous lists of putative causes of obesity – a list that now included 104 items. As he is careful to point out, “The links are not meant to be definitive or best study but merely a demonstration of the interest in the particular cause.” Given that many of these factors are implicated based largely on observational studies, which by their very nature cannot prove causality, some scepticism is in order. However, for many factors on this list there is biological plausibility, often backed by findings from animal or experimental studies. Here is Downey’s list of putative causes of obesity: 1. agricultural policies 2. air conditioning, 3. air pollution, 4. antibiotic usage at early age, 5. arcea nut chewing, 6. artificial sweeteners, 7.  Asian tiger mosquitos, 8. assortative mating, 9. being a single mother, 10. birth by C-section, 11. built environment, 12. celebrity chefs, 13. chemical toxins, (endocrine disruptors) 14. child maltreatment, 15. compulsive buying, 16. competitive food sales in schools, 17. consuming skim milk in preschool children, 18. consumption of pastries and chocolate (in Burkina Faso), 19. decline in occupational physical activity, 20. delayed prenatal care, 21. delayed satiety, 22. depression 23. driving children to school 24. eating away from home 25. economic development (nutrition transition) 26. entering into a romantic relationship, 27. epigenetic factors, 28. eradication of Helicobacter pylori, 29. family conflict, 30. family divorce, 31. first-born in family, 32. food addiction, 33. food deserts, 34. food insecurity, 35. food marketing to  children, 36. food overproduction, 37. friends, 38. genetics, 39. gestational diabetes, 40. global food system,(international trade policies) 41. grilled foods, 42. gut microbioata, 43. having children, for women, 44.  heavy alcohol consumption, 45.  home labor saving devices, 46. hormones (insulin,glucagon,ghrelin), 47. hunger-response to food cues, 48. high fructose corn syrup, 49. interpersonal violence, 50. lack of family meals, 51. lack of nutritional education, 52. lack of self-control, 53. large portion sizes, 54.  living in crime-prone areas, 55. low educational levels for women, 56. low levels of physical activity, 57. low Vitamin D levels, 58.  low socioeconomic status, 59. market economy, 60. marrying in later life 61. maternal employment, 62. maternal obesity, 63. maternal over-nutrition during pregnancy, 64. maternal smoking, 65. meat consumption, 66. menopause, 67. mental disabilities, 68. no or short term breastfeeding, 69. non-parental childcare 70. outdoor advertising, 71. overeating, 72. participation in Supplemental Nutrition Assistance Program (formerly Food Stamp Program) 73. perceived weight discrimination, 74. perception of neighborhood safety, 75. physical disabilities, 76. prenatal  maternal exposure to natural disasters, 77. poor emotional coping 78. sleep deficits, 79. skipping… Read More »

How Does Stress Affect Eating Behaviour?

One of the best recognized psychosocial factors tied to food intake is stress. However, this relationship is far from straightforward. While acute stress is often associated with loss of appetite, chronic stress is generally associated with an increase in appetite and weight gain. Now, a series of articles assembled in Frontiers in Neuroendocrine Science by Alfonso Abizaid1 (Carlton University, Canada) and Zane Andrews (Monash University, Australia), describe in detail the rather complex neuroendocrine factors that link stress to changes in ingestive behaviour. The series includes articles on the role of neuroendocrine factors like GLP-1, NPY, ghrelin, oxytocin, dopamin, and bombesin but also articles linking stress-related eating behaviours to adverse childhood experiences, perinatal influences, circadian rhythms and reward-seeking behaviours. I look forward to some interesting reads over the next few days and hope to summarize some of these articles in subsequent posts. @DrSharma Saint John, NB

How Does Bariatric Surgery Work?

Regular readers will be well aware of the fact that bariatric (unfortunately, often referred to as “weight-loss surgery”) is currently the most effective treatment for severe obesity. However, exactly why and how surgery works remains unclear. Earlier concepts of surgery working either because it creates a mechanical restriction to food intake and/or reduces caloric load due to malabsorption are not borne out by newer studies. Rather, it seems that complex neurohormonal changes together with often profound changes in ingestive behaviour act together to account for the resulting weight loss (and more importantly) for the long-term weight-loss maintenance. Just how many factors interact in specific and unspecific ways to lower body weight is now discussed in a review paper by Timothy Sweeney and John Morton, from Stanford University, in a paper published in Clinical Gastroenterology. As the authors discuss, there is a complex interaction between a wide range of factors including several hormones (leptin, ghrelin, adiponectin, glucagon-like peptide 1 (GLP-1), peptide YY, and glucagon), bile acid changes in the gut and the serum, and changes to the gut microbiome. The most profound changes in these systems are seen with the roux-en-Y gastric bypass, which induces large and distinctive changes in most measured fat and gut hormones, including early and sustained increase in GLP-1, possible through intestinal bile acid signaling. This may well explain why this operation appears to be the most effective and durable procedure. Clearly, hope remains that by better understanding the exact mechanisms through which surgery (which will only ever be available to a vanishingly small minority of people with excess weight) works, we will identify mechanisms and targets for desperately needed pharmacological treatments. @DrSharma Edmonton, AB

Hormonal Responses to Food Intake Begin in Your Mouth

In my current show at the 33rd Edmonton International Fringe Theatre Festival, I joke about the importance of chewing your food. This has classically been noted to be of importance to allow the enzymes in saliva to begin the process of digestion. However, now a fascinating study by Yong Zhu and colleagues from Iowa State University, published in Physiology and Behaviour shows that chewing prompts hormonal changes that vary based on the composition of the food. In their study, ten healthy males volunteers underwent a sham-feeding experiments (you chew but do not swallow your food) after an overnight fast with 3-min chewing of water, high-fat (nuts), high-carbohydrate (cereal) or high-protein (cheese) food provided in a randomized order (on four separate occasions). While plasma glucose levels increased slightly and plasma lipids decreased slightly after all test foods, the high-carbohydrate food elicited significantly higher insulin, and the high-protein food resulted in higher ghrelin compared to other test sessions. The authors attribute these changes in part to neuronal signals transmitted through the vagal nerve, which can for e.g. stimulate glucagon release, thereby explaining the observed increase in plasma glucose levels after all foods. This study shows that short-term oral exposure to different foods can result in metabolic and hormonal changes that are partly dependent on diet composition. If nothing else, this study points to the fact that chewing is not simply about mechanically preparing food for swallowing – it is far more a process that puts the organism into a nutritive state with distinct metabolic and hormonal changes. Chew your food! @DrSharma Edmonton, AB Zhu Y, Hsu WH, & Hollis JH (2014). Modified sham feeding of foods with different macronutrient compositions differentially influences cephalic change of insulin, ghrelin, and NMR-based metabolomic profiles. Physiology & behavior, 135, 135-42 PMID: 24952264   .

The Molecular Mechanism of Sleeve Gastrectomy

In recent year, vertical sleeve gastrectomy (VSG), which involves removing large parts of the stomach, thereby reducing it to the size of a small banana, has gained in popularity in bariatric surgery. Although slightly less efficacious, it is a far simpler procedure to perform than the “classic” Roux-en-Y gastric bypass. According to popular wisdom, the reason why VSG works has to do with mechanically reducing the volume of the stomach (thereby creating a physical “restriction”), whereby effect on gastric ghrelin secretion may or may not also play a role in reducing hunger (the science on this is somewhat unclear). Now, a paper by Karen Ryan and colleagues from the University of Cincinnati, published in Nature, provides a completely new explanation for the molecular mechanism by which this surgery appears to work. The study was prompted by the observation that VBG leads to profound changes in circulating bile acids. Bile acids are now known to bind to a nuclear receptor (farsenoid-X-receptor or FXR for short) which plays an important role in fat and glucose metabolism. Using a rather elegant series of studies in mice, Ryan and colleagues demonstrate that the weight loss effect of sleeve gastrectomy has little to do with reducing the size of the stomach. Rather, almost all of its effect on body weight appears to be mediated by the effect of this surgery on circulating bile acids and accompanying changes in gut microbial flora. The researchers also clearly demonstrate that much of the weight loss with SVG is dependent on a functional FXR, without which (as in FXR knockout mice) the surgery has little effect on body weight or glucose metabolism. This demonstration of the importance of bile acids and FXR signalling as an important molecular mechanism for why VSG actually works is important because it means that this surgery could possibly be mimicked by pharmacological interventions that target bile acid and/or FXR. In fact drugs that stimulate FXR (e.g. obeticholic acid) are already being considered for other indications including fatty liver disease and type 2 diabetes. Given the remarkable efficacy of VSG surgery, the possibility of providing the same benefits in a pill are clearly attractive. @DrSharma Edmonton, AB Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Pérez HE, Sandoval DA, Kohli R, Bäckhed F, & Seeley RJ (2014). FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature PMID: 24670636… Read More »