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Notably, in one of the largest GWAS in terms of both individuals and single nucleotide polymorphisms (SNPs) studied, the 97 loci associated with BMI that were identified were all expressed in the brain ( In patients with obesity, as a major consequence of gene-environment interactions, the homeostatic system is dysregulated and results in an increased food intake that sustains and maintains excess adiposity ( The pathophysiology of obesity is further operational in response to a weight loss, explaining why body weight tends to be regained over time

The mechanism is well established and has decades of consistent clinical evidence behind it

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Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-B activation in the nonhuman primate Macaca mulatta