How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

KEYPOINTS

• 01

  GLP-1 drugs push GLP-1 far above anything the body makes naturally

  GLP-1 drugs were first used for diabetes and only later became known for weight loss. Huberman notes they raise GLP-1 roughly a thousandfold above natural levels, and Kanoski agrees that is 'supra-physiological for sure.' What that means over the long term, good or bad, is still being worked out.

• 02

  GLP-1 receptors sit all over the brain, so the drugs may matter beyond appetite

  The receptors aren't limited to appetite and blood-sugar centers. They are dense in reward circuitry (the VTA, striatum and nucleus accumbens) and in the hippocampus, Kanoski's favorite region. Animal data support uses for substance-use disorders and possibly memory disorders and dementia. Human trials are only now coming out.

• 03

  Whether the drugs actually get into the brain is still disputed

  Rodent work from 2005–2012 on first-generation drugs suggested much of the appetite effect came from acting on the brain. Better tracer studies are now under way, using carbon-14-labeled peptides, from Elizabeth Rhea, Bill Banks and colleagues at the University of Washington. Early-generation drugs appear to enter the brain readily. For the newer drugs it's unclear, and where they act is not well understood.

• 04

  Natural GLP-1 works locally on the vagus nerve to end a meal

  L-cells in the intestine release GLP-1, which acts right next door (paracrine signaling) on GLP-1 receptors at the gut endings of the vagus nerve. The vagus carries 'within-meal' signals to the brainstem, the first brain site told that enough food has arrived. Kanoski calls GLP-1 one instrument in a 'symphony' of stomach-stretch and nutrient signals that produce fullness and stop eating. Neither man experiences 'food noise' himself, so they could only guess at what the drugs quiet.

• 05

  Your memory of a meal shapes hunger hours later

  Fullness right after eating follows what you actually ate, which Kanoski calls 'the wisdom of the body.' A few hours later, hunger ratings track what people think they ate. That makes the hippocampus, the brain's memory center, part of appetite control, not just a store of facts.

• 06

  A Western-style diet impairs hippocampal memory in animals quickly

  His lab's 'Western diet' gets about 35% of calories from fat and 15% from mostly simple sugars. In rodents it can impair hippocampus-dependent memory within about a week, though most studies run a few months. The hippocampus seems more vulnerable than other memory systems. Teenage exposure has been a major focus of his lab.

• 07

  Diet in midlife is linked to later dementia risk

  Human prospective studies link midlife diet and metabolic health, including visceral (belly) fat, to dementia risk. In mice engineered to develop Alzheimer's-like disease, a Western diet makes symptoms appear earlier. Kanoski sees diet as prevention across a lifetime rather than a treatment once symptoms start.

• 08

  Exercise can rescue diet-induced memory deficits in rats

  Rats switched from an unhealthy diet to a healthy one can keep long-lasting memory deficits, and exercise reversed them. Kanoski thinks the benefit comes partly from better metabolism and partly from direct changes in the brain.

• 09

  Gut signals reach the hippocampus through a three-step acetylcholine pathway

  Vagus nerve signals reach the brainstem, which projects to the medial septum. Acetylcholine-producing neurons there connect to the hippocampus. His lab is studying acetylcholine as the 'currency' of this gut–brain–memory link and asking whether disrupting the vagus nerve matters for Alzheimer's.

• 10

  Dopamine responses to sweet foods can be retrained

  Rats show a dopamine response to sucrose, or to a cue that predicts it. If sucrose is paired with a few minutes of drug-induced sickness, that response disappears. Kanoski calls this an extreme example of how flexible the reward system is. He notes that old punishment-based approaches in humans (shock, nausea) were unethical, and he knows of no good evidence they work, for example for quitting smoking.

• 11

  Oxytocin reduces eating mainly through the brainstem

  Oxytocin has long been known to suppress appetite. Work by Harvey Grill and others points to the brainstem as its strongest target. Oxytocin is made in the hypothalamus (the PVH) and released into the blood, and some oxytocin neurons project straight to the brainstem.