Hypothalamic Inflammation In Human Obesity
Friday, December 5, 2014
Regular readers may recall the exciting body of work from animal models of obesity showing that hypothalamic inflammation involving microscarring (gliosis) may play an important role in appetite and energy regulation in obesity.
Now, a study by Josep Puig and colleagues from the University of Girona, Spain, published in the Journal of Clinical Endocrinology and Metabolism, provides evidence for a similar process in humans.
The researchers used an MRI technique called diffusion tensor imaging (DTI) to measure hypothalamic damage in 24 consecutive middle-aged obese subjects (average BMI 43) and 20 healthy volunteers (average BMI 24).
Not only did the obese participants show greater signs of hypothalamic inflammation but these changes were also strongly associated with higher BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests.
While these studies do not prove cause and effect, these findings are consistent with findings in animal models and point to the role of pro-inflammatory pathways in the areas of the brain known to be intimately linked to appetite and energy regulation.
Understanding what exactly triggers this inflammatory response (in animal models, one fact appears to be a high-fat diet) and how this process could be inhibited, may open new avenues for obesity prevention and treatment.
@DrSharma
Madrid, Spain
Puig J, Blasco G, Daunis-I-Estadella J, Molina X, Xifra G, Ricart W, Pedraza S, Fernández-Aranda F, & Fernández-Real JM (2014). Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. The Journal of clinical endocrinology and metabolism PMID: 25423565
Friday, December 12, 2014
Interestingly, monounsaturated fat does not seem to trigger hypothalamic inflammation in rodent models. Excerpt:
Unlike SFAs, which stimulated microglial M1 activation in culture, in hypothalamic slices, and in the MBH of mice, monounsaturated FAs failed to do so in any context. By contrast, monounsaturates given i.v. or i.c.v. reduce food intake and hepatic glucose production in rodents, whereas SFAs do not. Therefore, whereas microglia sense SFA levels and transduce this into an inflammatory response, other cell types in the MBH may respond to monounsaturates. For example, neurons in the MBH are implicated in sensing FAs, and neuronal lipoprotein lipase may be needed for this sensing to occur. http://www.cell.com/cell-reports/fulltext/S2211-1247%2814%2900972-3
Of interest also is the fact that high carbohydrate intake is associated with high levels of serum SFA far more than high SF intake. Excerpt:
Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0113605