Abstract
The gluco-lipostatic theory and its modern variants assume that blood glucose and energy stores are controlled in closed-loop feedback processes. The Selfish Brain theory is based on the same assumptions, but additionally postulates that the brain, as an independent energy compartment, self-regulates its energy concentration with the highest priority. In some clinical situations these two theories make opposite predictions. To investigate one of these situations, namely caloric restriction, we formulated a hypothesis which, if confirmed, would match the predictions of the Selfish Brain theory—but not those of the gluco-lipostatic theory. Hypothesis: Calorie restriction causes minor mass (energy) changes in the brain as opposed to major changes in the body. We conducted a systematic review of caloric-restriction studies to test whether or not the evaluated studies confirmed this hypothesis. We identified 3,157 records, screened 2,804 works by title or abstract, and analyzed 232 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines, and the pre-defined hypothesis-decision algorithm), 8 papers provided enough information to decide on the hypothesis: In animals, high-energy phosphates were measured by 31P-nuclear magnetic resonance, and organ and total body weights were measured by scales, while in humans organ sizes were determined by magnetic resonance imaging. All 8 decidable papers confirmed the hypothesis, none spoke against it. The evidence presented here clearly shows that the most accurate predictions are possible with a theory that regards the brain as independently self-regulating and as occupying a primary position in a hierarchically organized energy metabolism.
Highlights
Most scientists support the theoretical notion that food intake is regulated by closed-loop feedback processes
Kennedy’s lipostatic theory gained momentum in the 1990s when leptin was identified as the substance from adipose tissue that he had suspected (Zhang et al, 1994)
Prior to our work on this systematic review, our protocol was registered on Prospero on 30th of January 2020, and an updated version was published on 28th of September 2020 (International prospective register of systematic reviews; CRD42020156816)
Summary
Most scientists support the theoretical notion that food intake is regulated by closed-loop feedback processes. Already in the 1950s, Mayer came up with the idea that blood glucose is the main regulated quantity in human energy metabolism (Mayer, 1953). Kennedy made a counterproposal (Kennedy, 1953). He believed that body weight was the regulated quantity. He postulated that a signal from the body energy stores controls food intake. Kennedy’s lipostatic theory gained momentum in the 1990s when leptin was identified as the substance from adipose tissue that he had suspected (Zhang et al, 1994)
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