Neuroplasticity in Obesity

Original Editor - Srishti Banerjee

Top Contributors - Kim Jackson, Lucinda hampton, Srishti Banerjee and Franca Ebomah  
Page Owner - Srishti Banerjee as part of the One Page Project

Introduction[edit | edit source]

Obesity leads to dysregulation of central neurocircuits which control autonomic, metabolic and cognitive function. It has been established that in response to high fat diet (HFD) there is activation of astroglia and neuroinflammation sets in which causes dysregulation of central neuro circuits which are involved in energy homeostasis before the development of obesity. Recent studies have shown that neuroinflammation sets in the areas regulating the food intake just after 1 day after the being exposed to HFD[1]

Astroglial Neuroplasticity[edit | edit source]

Astroglial modulation is done by brain derived neurotrophic factors(BDNF) which plays an important role in neural plasticity. Imaging studies have shown that obesity leads to reduced cortical thickness[2]which leads to neuronal reduction and impaired synaptic plasticity[3]similarly obesity can lead to age related white matter changes, poor cognition , impaired memory and learning[4][5]One of the mechanism which can be attributed all these changes is reduced levels and signalling of BDNF in obesity. Secondly cognitive decline and  impaired synaptic plasticity is attributed to systemic and central inflammation where proinflammatory cytokines, derived from the adipose tissues suppresses the neuronal function in brain. Astrocytic modulation of excitatory synaptic transmission leads to neuro degeneration and excitotoxicity throughout the CNS[6]

Changes in Brainstem[edit | edit source]

The brainstem undergoes neuroplastic changes in response to diet. It has been established that diet induced obesity (DIO) decreases the intrinsic excitability of vagal afferent and efferent neurons which also includes decrease in responsiveness of satiety peptides such as leptin , glucagon like peptide 1 , cholecystokinin. The decrease in afferent excitability decreases the meal induced mechanical and chemical stimulation and decrease in efferent excitability reduces the stomach tone and increases gastric and fasting volume. All this eventually increases the volume of food required for satiation therefore leading to an increased food intake and meal size which develops and maintains obesity[1]

Changes in Hypothalamus[edit | edit source]

Hypothalamus plays a critical role in controlling appetite, modulating neurocircuits affecting feeding behaviours, caloric intake and development of obesity[7]. Leptin plays a pivotal role in food intake and energy balance. Involvement of leptin in astroglial modulation is essentially important in food intake behaviors. Leptin enters the CNS via a saturable transport system and it acts within the hypothalamus to induce satiation and reduces the food intake. However exposure to HFD leads to hyperleptinemia which causes leptin insensitivity in the brain stem and hypothalamus.  This causes an energy imbalance, leading to increase in meal size , weight gain and obesity. In addition to this leptin resistance reduces the astrocytic release of ketone bodies from the hypothalamus leading to dysregulation of caloric intake and energy homeostasis[1]

Changes in Dorsal Striatum[edit | edit source]

Exposure to HFD causes changes in astrocytic signalling in dorsal striatum which leads to change in motor activity, food seeking behaviours and decision making.[1] [8]

Changes in Nucleus Accumbent (NAc)[edit | edit source]

Following exposure to HFD, neuroplastic changes takes place in the reward pathways of NAc through modulation of neuronal morphology[1][9]

Obesity Versus Addiction[edit | edit source]

Many imaging studies and literature reviews have found a link of similarity between DIO and addictive disorders. It has being established that the weight gain can be a result of addictive behaviours of food intake which include repeated food cravings , controlling food intake , inability to reduce the food intake despite of the negative consequences. Desire to lose weight has been compared to the attempts to quit addiction[10]Glutamatergic plasticity , dopamergic plasticity  and opioid changes are the changes which are common in substance abuse and obesity. Drug abuse and HFD both activates the mesolimbic nuclei i.e. NAc which is responsible for behavioural adaptations. In addition to the above mentioned alterations BDNF is associated with susceptibility to the drug seeking behaviour. Exposure to HFD leads to increase in BDNF in the NAc lysates which is associated with alteration in the reward signalling pathways[11]Several imaging studies have shown that there is reduced prefrontal activity in obese individuals which is quite similar to hypofrontal activity in addiction. PET scan studies shows a reduced cerebral blood flow in pre frontal cortex in response to a meal after 36 hour fast in obese women as compared to control. However these results are heterogeneous in nature.[12]

Dopaminergic changes occurring  are similar when exposed to HFD as they are in addiction. Dopamine regulates the glutamatergic plasticity. However it is seen that when exposed to HFD and drugs like cocaine and alcohol , the dopamine transmission gets altered which leads to alteration in dopamine- dependent straiatal glutamatergic plasticity. This includes increase in release of dopamine which over the time diminishes availability of dopamine receptors and dopamine reuptake is diminished. This leads to disruption of normal plasticity of the projections from the prefrontal cortex to NAc. This mechanisms form the basis of food choices and choice of physical inactivity in obesity[13][14]Apart from these changes, there is a different set of mechanism which is responsible for persistence of obesity.  There is alteration in synaptic plasticity due to fat , free fatty acids and triglycerides from the HFD. This includes disruption of hippocampal long term potentiation(LTP).  In addition to this obesity leads to inflammation of hippocampus  causing impaired hippocampal- dependent memory due to the disruption of neural networks of hippocampus[15]In addition to this persistent effects of obesity include alteration in gene expression which is quite similar to the changes in drug abuse. Inflammation in hypothalamus associated with obesity is linked with coexistence of depression in obesity15. Also the persistent effects of obesity include leptin and insulin resistance which form the basis of susatained changes in dopaminergic system[16]Therefore it can be concluded that neuroplasticity plays a pivot role in explanation of food intake habits , inability to curb the need to eat and futile attempts of weight loss in DIO.

Exercise induced neuroplasticity in obesity[edit | edit source]

Studies have shown that the exercises known to induce neuroplastic changes in obesity includes warm up and cool down exercises as per the principles of exercise therapy which is followed by exercises such as biking, running, and individualized strength training. It is important to enroll the individual for at least 60 minutes per session. However more evidence is required to generate a more detailed protocol to induce neuroplastic change.

Neuroplastic changes in response to exercise[edit | edit source]

In response to exercise changes are seen in BMI, serum concentration of leptin, BDNF levels which is known to moderate neuroendocrine and metabotrophic processes which leads to a reduced food intake and improves glucose metabolism and insulin sensitivity and HDL-C. Changes in brain in response to exercise includes increase in gray matter density in left hippocampus , left insular cortex , and left inferior cerebellum[17][18] [19][20][21]Exercise leads to generation of low oxidative stress which has positive effect on all the cell systems. In response to exercise a cascade of processes is initiated which is important in repair , remodeling and reshaping processes which improves the ability of cellular systems to handle the free radicals[22] [23][24]

Exercise has shown to reverse alteration in diffusion parameters which eventually restores obesity related regional white matter changes.[25]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 ClyburnC , Browning KN. Role of astroglia in diet induced central neuroplasticity J Neurophysiology 121:1195-1206, 2019 doi:10.1152/jn.00823.2018
  2. ↑ Marqués-Iturria, I.; Pueyo, R.; Garolera, M.; Segura, B.; Junqué, C.; García-García, I.; Sender-Palacios, M.J.; Vernet-Vernet, M.; Narberhaus, A.; Ariza, M.; et al. Frontal cortical thinning and subcortical volume reductions in early adulthood obesity. Psychiatry Res. 2013, 214, 109–115
  3. ↑     Gazdzinski S ,Kornak J , Weiner , M. W , Meyerho , D.J , Body mass index and magnetic resonance markers of brain integrity in adults. Ann.Neurol. 2008 63, 652–657
  4. ↑ Prickett , C; Brennan ,l Stolwyk , R. Examining the relationship between obesity and cognitive function : A systematic  literature review Obes. Res. Clin: Pract 2015 , 9, 93-113.
  5. ↑     Sophia X. Sui, Michael C.Ridding and Brenton Hordacre : obesity is associated with reduced plasticity of the human cortex. Brain Sci 2020 , 10 , 579; doi:10.3390/brainsci10090579
  6. ↑ Lee , E.B ; Mattson , M.P. The neuropathology of obesity : Insights from human disease. Acta Neuropathology . 2014, 127, 3–28
  7. ↑    King P.J. The hypothalamus and obesity. Curr Drug targets 223-240, 2005 . doi:10.2174/1389450053174587
  8. ↑     Fritz BM,Munoz B, Yin F, Bauchle C , Atwood Bk , A high- fat , high sugar western diet alters dorsal striatal glutamate , opioid and dopamine transmission in mice. Neuroscience 372 : 1-15, 2018 . doi:10.1016/j.neuroscience.2017.12.036.
  9. ↑    Gutierrez-Martos M, Girard B, Mendonaca – Netto S, Perroy J, Valient E, Maldonado R , Martin M. Cafeteria diet induces neuroplastic modifications in nucleus accumbens mediated by microglial activation. Addict Biol 23: 735-749, 2018  . doi:10.1111/adb.12541
  10. ↑     Davis C , et al. Evidence that ‘ food addiction’ is a valid phenotype of obesity. Appetite. 2011; 57:711-717. DOI: 10.1016/j.appet.2011.08.017 [PubMed: 21907742]
  11. ↑     Bridget A.Matikainen-Ankney and Alexxai V. Kravitz. Persistent effects of obesity : a neuroplasticity hypothesis Ann N Y Acad Sci. 2018 September ; 1428(1): 221–239. doi:10.1111/nyas.13665.
  12. ↑     Le DS , et al. Lessactivation in the left dorsolateral prefrontal cortex in the reanalysis of the response to a meal in obese than in lean women and its association with successful weight loss. The American journal of clinical nutrition 2007 ; 86:573–579. [PubMed: 17823419]
  13. ↑ Bridget A.Matikainen-Ankney and Alexxai V. Kravitz. Persistent effects of obesity : a neuroplasticity hypothesis Ann N Y Acad Sci. 2018 September ; 1428(1): 221–239. doi:10.1111/nyas.13665
  14. ↑     Carlin JL, et al. removal of high fat diet after chronic exposure drives binge behaviour and dopaminergic dysregulation in female mice. Neuroscience. 2016 , 326:170–179. DOI: 10.1016/j.neuroscience.2016.04.002 [PubMed: 27063418]
  15. ↑     MillerAA, spencer SJ. Obesity and neuroinflammation : a patheay to cognitive impairment. Brain , behaviour and immunity. DOI: 10.1016/j.bbi.2014.04.00
  16. ↑   Ye  J. Mechanisms of insulin resistance in obesity. Frontiners of Medicine. 2013; 7:14–24. DOI: 10.1007/s11684-013-0262-6 [PubMed: 23471659]
  17. ↑ Tsuchida, A., Nonomura, T., Ono-Kishino, M., Nakagawa, T., Taiji, M., and Noguchi, H. (2001). Acute effects of brain-derived neurotrophic factor on energy expenditure in obese diabetic mice. Int. J. Obes. Relat. Metab. Disord. 25, 1286–1293. doi: 10.1038/sj.ijo.0801678
  18. ↑ Nakagawa, T., Ono-Kishino, M., Sugaru, E., Yamanaka, M., Taiji, M., and Noguchi, H. (2002). Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes Metab. Res. Rev. 18, 185–191. doi: 10.1002/dmrr.290
  19. ↑ Lebrun, B., Bariohay, B., Moyse, E., and Jean, A. (2006). Brain-derived neurotrophic factor (BDNF) and food intake regulation: a minireview. Auton. Neurosci. 126, 30–38. doi: 10.1016/j.autneu.2006.02.027
  20. ↑ Yamanaka, M., Itakura, Y., Ono-Kishino, M., Tsuchida, A., Nakagawa, T., and Taiji, M. (2008). Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice. J. Biosci. Bioeng. 105, 395–402. doi: 10.1263/jbb. 105.395
  21. ↑ Tsao, D., Thomsen, H. K., Chou, J., Stratton, J., Hagen, M., Loo, C., et al. (2008). TrkB agonists ameliorate obesity and associated metabolic conditions in mice. Endocrinology 149, 1038–1048. doi: 10.1210/en.2007-1166
  22. ↑ Arumugam, T. V., Gleichmann, M., Tang, S. C., and Mattson, M. P. (2006). Hormesis/preconditioning mechanisms, the nervous system and aging. Ageing Res. Rev. 5, 165–178. doi: 10.1016/j.arr.2006.03.003
  23. ↑ Radak, Z., Chung, H. Y., and Goto, S. (2008). Systemic adaptation to oxidative challenge induced by regular exercise. Free Radic Biol. Med. 44, 153–159. doi: 10.1016/j.freeradbiomed.2007.01.029
  24. ↑ Whiteman, A. S., Young, D. E., He, X., Chen, T. C., Wagenaar, R. C., Stern, C. E., et al. (2014). Interaction between serum BDNF and aerobic fitness predicts recognition memory in healthy young adults. Behav. Brain Res. 259, 302–312. doi: 10.1016/j.bbr.2013.11.023
  25. ↑ Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M, Stumvoll M, Villringer A and Pleger B (2015) Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front. Hum. Neurosci. 9:372. doi: 10.3389/fnhum.2015.00372
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