Monday, August 18, 2014

Science of Nutrition Podcast

I recently did an interview with Seth Yoder, who has a master's degree in nutrition science and writes the blog The Science of Nutrition.  Seth caught my attention recently with his withering review of The Big Fat Surprise, the latest book to claim that ideological/incompetent scientists and public policy makers got the science of nutrition backward and we should all be eating low-carb, high-fat, high-meat diets.  I was impressed by how deeply Seth dug into the reference list, and how well he picked up on subtle but troubling misrepresentations of the evidence.

Last week, Seth and I got together at a local brewpub to do an interview.  We were joined by Carrie Dennett, an MPH/RDN who has a nutrition blog and writes for the Seattle Times.  I'd probably do a lot more interviews if I could ride my bike to them and have my interviewer buy me a drink.

Speaking of drinks, by the end of the interview I had a little buzz-- you might hear it in my voice if you listen closely.  As usual, I had plenty to say about body fat regulation, food reward, and other topics, with plenty of side trips to discuss particularly fascinating studies.  Also, the word of the day was 'compelling'.

Enjoy the interview!

Tuesday, August 5, 2014

Can Hypothalamic Inflammation and Leptin Resistance be Reversed?

A new study by yours truly begins to address the key question: can hypothalamic inflammation and leptin resistance be reversed?

Leptin is the primary hormonal regulator of body fatness in the human body (1).  Secreted by fat tissue, it acts in many places in the body, but its most important effects on body weight occur via the brain, and particularly a brain region called the hypothalamus.  The hypothalamus is responsible for keeping certain physiological variables within the optimal range, including blood pressure, body temperature, and body fatness.

In obesity, the brain loses its sensitivity to leptin, and this causes the body to begin 'defending' a higher level of body fatness, analogous to how a person with a fever 'defends' a higher body temperature (1).  Once a person has become obese, it's difficult to return to true leanness because this system vigorously opposes major fat loss.  Leptin resistance makes fat loss more difficult.

In rodent models, leptin resistance is caused at least in part by inflammatory signaling in the hypothalamus.  We can observe this in multiple ways, but one common way is to look at the appearance of specific cells in the brain that change number, size, and shape when inflammation is present (2).  These cells are called microglia and astrocytes.  In addition to the work in rodents, we've published preliminary evidence that these same inflammatory changes occur in the hypothalamus of obese humans (2).

A key question is whether or not these inflammatory changes can be reversed.  Is a person with leptin resistance doomed to have it forever, undermining fat loss efforts for the rest of his or her life?  Or can it be corrected, possibly allowing easier and more sustainable fat loss?  We just published a study in Endocrinology that begins to answer this question, using a mouse model of dietary obesity (3).  I'm co-first author of this study along with my colleague Kathryn Berkseth, MD.  My former mentor Mike Schwartz, MD is senior author.

The Study

Read more »

Friday, August 1, 2014