Does Your Liver Control Your Appetite?
The answer may well be “yes”, at least if you happen to be a mouse. In a rather exciting study by Iliana López-Soldado and colleagues from the Institute for Research in Biomedicine, Barcelona, published in DIABETES, the researchers show that increased liver glycogen content may affect appetite (measured as food intake) and otherwise have beneficial effects on metabolism. In their experiments, the researchers used genetically modified mice, which overexpress an enzyme (PTG) resulting in increased liver glycogen. Not only did these animals reduce their food intake when fed a high fat diet, they also did not develop the typical glucose intolerance, elevated insulin levels and fatty liver seen in normal mice on this diet. Apart from losing weight (associated with lower leptin levels), these animals also had lower expression of neuropeptide Y (NPY) and higher expression of propiomelanocortin (POMC) in the hypothalamus. Thus, the authors summarize their findings as follows: :…liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of a HFD and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity.” As a number of compounds exist that may do exactly that, these studies may point to a novel pathway for the pharmacological treatment of obesity – but let’s keep in mind that the road from finding in mice to effective treatments in humans is a long and thorny road. @DrSharma Edmonton, AB López-Soldado I, Zafra D, Duran J, Adrover A, Calbó J, & Guinovart JJ (2014). Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model. Diabetes PMID: 25277398 .
Does Maternal Obesity Affect the Gut Microbiome of the Offspring?
Yesterday, I blogged about the Maternal Resource Hypothesis, proposed by Edward Archer, as a driver of childhood obesity. Today’s post is about another interesting finding by Jeffrey Galley and colleagues from Ohio State University, published in PLOS one, suggesting that maternal obesity may be associated with differences in the gut microbiome in children in early life. The researchers compared the gut bugs from fecal samples from children 18–27 months of age (n = 77) born to obese or non-obese mothers. At least in women of higher socioeconomic status, offspring of obese mothers showed significant differences in their gut bacteriome from those of non-obese mothers in a manner that has been previously linked to differences in weight and diet (differences were noted in the abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp). While these findings were limited to women of higher socioeconomic status, the authors do not have a ready explanation for these findings. Their best guess is that perhaps the etiology of obesity may differ between women of higher and lower socioeconomic status and it may well be that the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. It is unlikely that dietary differences explain these findings: “In our sample, we found no differences in the children from obese and non-obese mothers in terms of breastfeeding behavior, age at which solid foods were introduced, or the current frequency of consumption of meat, vegetables, and cereals/grains regardless of maternal SES. This suggests that diet did not explain the observed differences in the children’s gut microbiome related to maternal obesity and SES.” Indeed, the authors are quick to point out that further research is needed to better understand the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course of the offspring: “The potential role of the gut microbiome in this intergenerational transmission of obesity risk warrants further attention. In particular, the stability of such effects into later childhood and adolescence, the clinical relevance of abundances of specific bacteria in conferring risk for obesity, and the ultimate impact of early life microbial profiles on long-term weight trajectory remains to be explicated.” Nevertheless, these findings are intriguing in that they suggest a link between maternal obesity and the possible transmission of obesogenic microbes to their offspring. @DrSharma Vancouver, BC Galley JD, Bailey M, Kamp Dush C, Schoppe-Sullivan S, & Christian LM (2014). Maternal… Read More »
Are Sedentary Moms Promoting Childhood Obesity?
Last week, Edward Archer from the University of Alabama at Birmingham (UAB), published a paper in the Mayo Clinic Proceedings (to much media fanfare), suggesting that the primary driver of childhood obesity is the shifting of nutrient energy to fetal adipose tissue as a result of increased maternal energy availability paired with decreased maternal energy expenditure, resulting in fetal pancreatic b-cell and adipocyte hyperplasia – a theory, which Edwards labels the “maternal resource hypothesis”. The primary process for these changes, as readers of these pages will have read before, is through epigenetic modification of DNA, which, together with other non-genetic modes of transmission including learned behaviours and environmental exposures (socioenvironmental evolution), leads to “phenotypic evolution”, which Edward describes as, “…a unidirectional, progressive alteration in ontogeny that is propagated over multiple successive generations and may be quantified as the change over time in the population mean for the trait under examination (eg, height and obesity).” Since the beginning of the 20th century, socioevironmental factors have significantly altered the energy balance equation for humans “Socioenvironmental evolution has altered the evolution of human energy metabolism by inducing substantial decrements in EE imposed by daily life while improving both the quality and the quantity of nutrient-energy availability.” “For example, as thermoneutral environments became ubiquitous, the energy cost of thermoregulation declined, and improved sanitation (eg, clean water and safer food) and vaccinations decreased the energy cost of supporting parasites (eg, fleas) and resisting pathogens (eg, communicable diseases and diarrheal infections).” Over the past century, these developments have led to profound phenotypic changes including, “progressive and cumulative increases in height, body stature and mass, birthweight, organ mass, head circumference, fat mass/adiposity as well as decreases in the age at which adolescents attain sexual maturity…” Archer goes on to describe some of the many factors that may have changed in the past century, whereby, he singles out sedentariness as one of the key drivers of these developments (not surprising given Archer’s background in exercise science). Thus, although one could perhaps make very similar arguments for any number of factor that may have changed in the past century to, in turn, affect insulin resistance and ultimately energy partitioning (change in diet, sleep deprivation, increasing maternal age, endocrine disruptors, antibiotic use, gut microbiota, medication use and many other factors I ca think of), Archer chooses to elevate sedentariness to being the main culprit. While this may or may not be the full… Read More »
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