NEUROENERGETICS Carbohydrate-biased control of energy metabolism: the darker side of the selfish brain Tanya Zilberter* Infotonic Consultancy, Stockholm, Sweden *Correspondence: zilberter@gmail.com INTRODUCTION There is evidence that the brain favors con- sumption of carbohydrates (CHO) rather than fats, this preference resulting in glyco- lysis-based energy metabolism domination. This metabolic mode, typical for consumers of the “Western diet” (Cordain et al., 2005; Seneff et al., 2011), is characterized by over-generation of reactive oxygen species and advanced glycation products both of which are implicated in many of the neuro- degenerative diseases (Tessier, 2010; Vicente Miranda and Outeiro, 2010; Auburger and Kurz, 2011). However, it is not CHO but fat that is often held responsible for metabolic pathologies. This paper, based on analysis of experimental data, offers an opinion that the obesogenic and neurodegenerative effects of dietary fat in the high-fat diets (HFD) cannot be separated from the effects of the CHO compound in them. Since this is not a comprehensive literature review, only essential research results are presented. It is general knowledge that the glucose homeostasis possesses very limited buffer- ing capacities, while energy homeostasis in its fat-controlling part enjoys practically unlim- ited energy stores. Logically, a control sys- tem with a limited buffer should thoroughly defend the “consumption” part. Indeed, existing experimental data (briefly reviewed here later) show important properties of the CHO intake control that is different from or not shown for the fat intake control: (1) A mere oral sensation of CHO elicits physiological anticipation response (cephalic phase) that is either inborn or rapidly conditioned. (2) Oral CHO sensation stimulates reward-specific brain areas. (3) CHO addiction is essentially similar to typical drug addictions. These peculiarities can explain the physi- ologically and metabolically opposite effects of obesogenic HFD versus the ketogenic diet (KD), which is also HFD but lower in CHO. THE SELFISH BRAIN CONCEPT: TWO MEANINGS There are two ways to look at the CHO- biasing trait of the brain. (1) The “Selfish Brain” is a term coined by Robert L. DuPont in the title of his book where he wrote: “With respect to aggression, fear, feeding, and sexuality, the brain is selfish. It sim- ply wants what it wants right now” (DuPont, 1997). We must add, “if the environment permits, the brain gets it.” The bad news is, in the long run the body can be harmed as the result. (2) An elaborate (and rare for modern physiology) systemic concept explai- ning the fundamental ability of the brain to control priorities of energy allocation has been proposed by Peters and colleagues who also tit- led their theory the Selfish Brain. They wrote referring to DuPont’s book: “The brain looks after itself first. Such selfishness is reminiscent of an earlier concept in which the brain’s selfishness was addressed with respect to addiction. We chose our title by analogy but applied it in a different context, i.e., the compe- tition for energy resources” (Peters et al., 2004). These two meaning of the Selfish Brain have important common points if we con- sider the addiction (highly non-homeo- static) as a result of the “push” principle borrowed from the economic “push–pull” paradigm of supply chains. As early as in 1998, Hill and Peters wrote: “According to the ‘push’ principle, the environment pushes excess amounts of energy into the organism” (Hill and Peters, 1998). They also share a common mechanism – reward. According to DuPond, “What makes a drug addictive is not that it is ‘psy- choactive’ but that it produces specific brain reward. It is not withdrawal that hooks the addict, it is reward” (DuPont, 2008). This reward is hard-wired in the brain, in the loci where both “pull” and “push” systems might be converging, something that is dis- cussed within the Selfish Brain paradigm as the comforting effect of food (Peters et al., 2007), particularly, the CHO-rich foods (Hitze et al., 2010). PUSH AND PULL PARTS OF ENERGY SUPPLY CONTROL SYSTEM The role of depots, as determined by a gen- eral principle in economic supply chains, is energy buffering in unstable environments (Fischer et al., 2011). Peters and Langemann (2009) analyzed two concepts of environ- ment–organism relationship with opposite views at depots: (1) An environment offering abundant energy beyond homeostatic need “pushes” it into the body via some evolutionary appropriate gateway. The surplus, naturally, goes into depots. Peters and Langemann, howe- ver, remained in doubt about this concept partly due to the fact that this “push” does not work invariably for all animal or human subjects (Martin et al., 2010; Cao et al., 2011). (2) A somewhat alternative concept, well accepted for the last 50 years, con- cerns the “pull” character of the open system “organism–environment,” supposedly in accordance with home- ostatic needs. In this system, either the size of fat depot (Kennedy, 1953; Woods and Ramsay, 2011) or glu- cose levels (Mayer, 1953) are being controlled. The role of CHO depot was not con- ferred, perhaps due to its negligible storing capacities. Indeed, the sizes of CHO and fat depots are incomparable. In the sur- vival terms, CHO can provide energy sup- port for less than 2 days (Bilsborough and Crowe, 2003), while a year-long complete Frontiers in Neuroenergetics www.frontiersin.org December 2011 | Volume 3 | Article 8 | 1 OPINION ARTICLE published: 20 December 2011 doi: 10.3389/fnene.2011.00008