Many of the ideas in our paper will be familiar to those who follow this blog, but most of it is more technical than I can get away with here. One of the central concepts is that body fatness is actively regulated by the brain, rather than simply being the passive result of voluntary eating and exercise behaviors. This is supported by a massive amount of evidence spanning the last 170 years (2). Obesity involves the brain 'defending' a higher level of fat mass. Another central concept is that the brain regions that regulate food intake and body fatness are reciprocally interconnected with those that respond to food reward/palatability, and highly rewarding/palatable food can increase food intake and body fatness by this mechanism. Although I didn't invent the concept (I think Dr. Michel Cabanac may have invented it in the 1970s), I've never seen the supporting evidence laid out like this in a modern review article, so I think it will be novel for many people even within my field. Unfortunately, space didn't permit me to expand on it nearly as much as I wanted, but for those who would like more detail on this particular concept, please see the articles I wrote in October (3, 4).
Here are a few quotes from the paper. From the introduction:
Over the course of industrialization, affluent populations have experienced an “epidemiological transition” characterized by an increased prevalence of certain disorders that are uncommon both in nonindustrial populations and in wild animals (1). Among these, obesity is perhaps the most conspicuous. Affecting approximately one third of adults in the United States (with an additional one third falling into the overweight category) (2), obesity has become a leading cause of morbidity, mortality, and reduced quality of life (3), a problem aggravated by the limited efficacy of nonsurgical treatments.In the first section, we comment on the role of blood glucose and insulin levels in feeding behavior, which is widely misunderstood:
Nearly 60 yr ago, Jean Mayer and his contemporaries hypothesized that because hypoglycemia potently stimulates appetite, hunger is normally triggered by sensing of declining plasma glucose levels or rates of glucose utilization by hypothalamic “feeding centers” (8). Decades of subsequent research have demonstrated that to the contrary, meal onset is not causally related to preprandial blood glucose (or insulin) levels within the normal physiological range (9). Yet the notion that low glucose (or elevated insulin) levels drive feeding behavior and promote fat gain remains widely popular, due largely to the marketing of commercial diet plans based on the glycemic index or reduced carbohydrate content.A quote from the sections describing the impact of excessive food reward/palatability on body fatness:
These findings collectively suggest that obesity can arise when animals or humans are confronted with foods whose palatability/reward value greatly exceeds that to which they are genetically adapted, and hence that interventions that inhibit food reward can prevent fat gain and promote fat loss. In considering these hypotheses, it is important to bear in mind that obesity in both humans and animal models involves the biological defense of an elevated level of body fat mass (Fig. 3). A key issue, therefore, is to understand how a change in the reward value of a diet impacts the energy homeostasis system.We also discuss the central role of leptin in body fat regulation, the fascinating case of bariatric surgery, genetic and developmental factors in obesity, and of course the role of inflammation and neuron injury in the hypothalamus.
I'm grateful to Dr. Schwartz and JCEM for the opportunity to publish this article. I look forward to feedback from researchers, physicians and anyone else who reads it.