lect 11-27-23diet-exc.pdf

The impact of diet and exercise on brain and body Fernando Gomez-Pinilla, Ph.D. • Diet and exercise are major modulators of health • Multiple effects across brain and body • Cell metabolism underlies effects of diet and exercise on cognitive abilities The modern brain evolved on healthy eating an...

The impact of diet and exercise on brain and body Fernando Gomez-Pinilla, Ph.D. • Diet and exercise are major modulators of health • Multiple effects across brain and body • Cell metabolism underlies effects of diet and exercise on cognitive abilities The modern brain evolved on healthy eating and exercise: healthy diet and exercise became necessary for survival Lots of exercise Larger brain than preys to compete for survival Natural food F. Gomez-Pinilla, UCLA From Delson et al. Encyclopedia of Human Evolution and Prehistory, Garland Publishing, 2000, p529 Fernando Gomez-Pinilla, UCLA Efficient use of energy crucial for brain evolution and function Exercise and food act as Epigenetic Modifiers Primitive Brain Extensive Gene Reprogramming Larger, more efficient Brain Neuronal susceptibility to metabolic alterations influencing health and disease • The human brain consumes 20–25% of the total energy spite of small relative size to body. • No surprise that the pathogenesis of many neurological disorders has an energy component Cell bioenergetics modulates health status Diabetes, obesity healthy Fontana, Science, 2010 Top 10 leading causes of death in US, 2010 Heart disease Cancer Respiratory diseases Stroke Accidents Alzheimer’s disease Diabetes Kidney Diseases Influenza & pneumonia Suicides Fernando Gomez-Pinilla, UCLA Metabolic disorders such as diabetes reduce brain capacity and increases risk of neurological disorders • Diabetes and obesity are risk factors for demyelinating disorders such as Multiple Sclerosis (Oliveira, Nutrition, 2014; Hou, J Epidemiol., 2017) • Chronic obesity is associated with structural brain changes (Ho et al, Neurobiol Aging, 2010; Raji et al, Human Brain Map, 2010; Bryan et al, Radiology 2014). • Increased risk for neurological and psychiatric disorders (Am J Manag care 2007, 13 (7). • Diabetes is a significant predictor of poor outcome in neurological disorders such as Alzheimer’s (Profeno, Biol Psych.,2010) and trauma (Ley J, J Trauma 2011) • Rise in consumption of sugars associated with the increased incidence of obesity in the general population (Hu & Malik, 2010; Malik et al., 2010) Fernando Gomez-Pinilla, UCLA Too much fructose consumption reduces the substrates for learning and memory Synaptic structure Fernando Gomez-Pinilla, UCLA Cisterna et al., BBADIS, 2015 Saturated fats and sugars, not brain food • Associated to obesity and metabolic syndrome • Increases risk for Alzheimer’s disease • Increases risk for depression and mood disorders • Reduces brain resilience F. Gomez-Pinilla, UCLA Whole food (and exercise) better than pills Exercise and diet impact multiple molecular systems in brain and body which maintain homeostasis Ding et al., Eur. J. Neuroscience, 2006 F. Gomez-Pinilla, UCLA Gomez-Pinilla, Nature Rev. Neurosci, July 2008 Fernando Gomez-Pinilla, UCLA Marx et al., Mol Psychiatry. 2020 Nov 3. The brain power of Omega 3 fatty acids • DHA is part of the structure of brain (~31% of FA in PE in cortex) -- plasma membranes, particularly at synaptic terminals • DHA is important for neuronal communication and processing of information, learning and memory, emotions, and protects against neurodegeneration • Body and brain is inefficient to synthesize Omega-3 fatty acids • Linolenic acid (18:3 n-3) >>>docosahexanoic acid (DHA, n-3) • DHA is crucial in brain/retina development and CNS maintenance • DHA insufficiency compromises membrane fluidity and neuronal signalling Brainfood Fernando Gomez-Pinilla, UCLA Fernando Gomez-Pinilla, UCLA Latency (sec) BDNF (% of RD) Exercise helps counteract effects of unhealthy diets: restoring BDNF and cognitive loss * * 200 * 150 100 17.5 50 15 0 * RD HF 12.5 10 RD/exercise 7.5 HF/exercise 5 2.5 1 2 3 1 month 1 2 3 2 months Days of trial Diet period Molteni et al, Neuroscience., 2004 Exercise improves brain function • Decreases anxiety: affects several neurotransmitters associated with emotions such as dopamine, norepinephrine, serotonin and acetylcholine • Improves focus and concentration, reaction times • Promotes growth of new brain cells • Protect brain from aging and neurodegenerative diseases • Can regularize sleep • Exercise has the capacity to restore energy homeostasis and influence many organs and tissues Fernando Gomez-Pinilla, UCLA Exercise reduces cognitive impairment in aging Exercise increases cortical volume in humans   Fitness training reduces cognitive decline associated with aging and increases brain volume in selected areas (Kramer, 2004, 2005). High impact running improves learning in young subjects (Winter, 2007). Hillman et al, Nature Rev Neurosci, 2008 F. Gomez-Pinilla, UCLA Aerobic Fitness & Achievement Test Performance Total ISAT Score 400 350 300 250 2 200 R = 0.22 0 10 20 30 40 50 PACER (# Laps) Castelli, Hillman, Buck, & Erwin (2007) JSEP. 60 70 80 How diet and exercise affect cognitive capacity? Cognitive reserve: saving in brain bank for rainy days Multiple effects in CNS and periphery Collaborative effects of diet and exercise promoting membrane homeostasis and neuronal signaling Induction of molecules related to synaptic plasticity and energy metabolism Membrane homeostasis, supporting signaling and information processing Epigenetic regulation supporting stable changes in genome Gomez-Pinilla, Nature Rev. Neurosci, July 2008 Exercise affects many proteins, neurotransmitters, hormones across brain and body Most genes and proteins associated with with energy regulation Redox regulation 3% Others 10% Energy metabolism 43% Plasticityrelated 44% Ding et al., Eur. J. Neuroscience, 2006 Gomez-Pinilla, Nature Rev. Neurosci, July 2008 Fernando Gomez-Pinilla, UCLA Fernando Gomez-Pinilla, UCLA • A large number of neuropsychiatric disorders are the result of complex interactions between genetic factors and the environment (Dauncey, 2012) and that epigenetic mechanisms may mediate these effects (Choi and Friso, 2010). Epigenetic memory • Exercise and feeding are one of the most crucial factors for species survival and adaptation, and they have the potential to influence the brain by building an “epigenetic memory” that could provide resistance to neurological challenges. • Epigenetic modifications of DNA and RNA provide with an opportunity to save experience for “rainy days” • This epigenetic memory provides an underlying mechanism for the process by which the brain builds up cognitive reserve to resist periods of hardship. Fernando Gomez-Pinilla, UCLA EPIGENETICS: The program of genes (epigenome) can be changed by the environment, altering the course of health or disease Fernando Gomez-Pinilla, UCLA How healthy foods interact with unhealthy foods to affect brain plasticity and function? High caloric (Saturated fat and sugars) Omega-3 fatty acids exercise Fernando Gomez-Pinilla, UCLA