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Treatment Options for Chemical Sensitivity
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
In contrast to the role of autophagy in clearing lipid droplets from the liver, autophagy is required for the production of the large lipid droplets characteristic of white adipose tissue.214,215 White adipose refers to the canonical fat storage tissue that expands in obesity. This tissue is a parking place for many toxic chemicals. When the fat is broken up, the toxics are released and the health of chemically sensitive patient is temporarily worsened. This white fat is in contrast to brown adipose tissue, a mitochondria-rich tissue that catabolizes glucose and lipids to generate heat rather than ATP. It appears damaged in chemically sensitive patients, who are always cold and have normal thyroid. Brown adipose tissue contains uncoupling protein 1, which allows protons to leak across the inner mitochondrial membrane, short-circuiting oxidative phosphorylation. Inhibition of autophagy blocks white adipocyte differentiation, and adipose-specific knockout of atg7 results in mice whose white adipocytes manifest features typical of brown adipose tissue. Consistent with the rapid energy burning of brown adipocytes, these mice are lean; however, they are not healthy—when fed either a regular or high-fat diet, they are at increased risk of early death.214
Organic Chemicals
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
Alternatively, activated M2 macrophages are also an indispensable component of the nonshivering thermogenic response of brown adipose tissue (BAT), the sole dedicated thermogenic tissue in mammals.468 Cold exposure elicits this response via hypothalamic stimulation of BAT-innervating efferents of the sympathetic nervous system that, in turn, activates brown adipocytes by releasing catecholamines. Once activated, brown adipocytes oxidize fatty acids and dissipate the resulting mitochondrial proton gradient via uncoupling protein-1, liberating heat.468 Alternative MS macrophages form an indispensable component of this adrenergic synapse, accounting for ∼50% of the total catecholamine content of cold-stimulated brown and WATs.468 In response to cold exposure, alternative M2 macrophages produce catecholamines, which together with sympathetic efferents induce the thermogenic program in brown adipocytes while simultaneously inducing lipolysis in adipocytes.468 Disinterage animals lacking alternative M2 macrophages are thus unable to mount an effective thermogenic response or mobilize the fatty acids necessary to support it.
Mitochondrial uncoupling protein 2 is regulated through heterogeneous nuclear ribonucleoprotein K in lead exposure models
Published in Journal of Environmental Science and Health, Part C, 2020
Gaochun Zhu, Qian Zhu, Wei Zhang, Chen Hui, Yuwen Li, Meiyuan Yang, Shimin Pang, Yaobing Li, Guoyong Xue, Hongping Chen
Recent studies have showed that uncoupling protein 2 (UCP2) is vital for the adaptation of synaptic plasticity in learning and memory.14 UCP2 is a member of mitochondrial uncoupling proteins (UCPs) which include UCP1, UCP2, UCP3, UCP4 and UCP5. UCP2 is abundantly expressed in hypothalamic nuclei, substantia nigra, and especially in the hippocampus of rats.14 UCP2, an inner mitochondrial membrane anion carrier which is encoded by nuclear genome but functions exclusively in mitochondria,15 is activated by free radicals and free fatty acids.16 And UCP2 plays an important role in uncoupling oxidative phosphorylation from ATP synthesis via controlling proton reentry into the mitochondrial matrix. Therefore, uncoupled neurons can adapt rapidly and efficiently changeable neuronal activities through regulating synaptic plasticity.14 Recently, UCP2 has been shown to play a critical role in protecting the body from neurological diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, temporal lobe epilepsy, brain trauma, stroke and ischemia.14,16–19. Taken together, UCP2 can affect synaptic plasticity and neurodegenerative processes, and maintain learning and memory functions in the hippocampus by regulating mitochondrial biogenesis, calcium efflux, free radical production and local temperature.20 But the mechanism that regulates its expression in lead exposure models remains to be illuminated.