Journal of Advanced Clinical Neurology Research

Abstract

Introduction: The coexistence of obesity and type 2 diabetes mellitus (DMT2), clinically termed "diabesity," represents one of the most critical challenges to contemporary public health. The low success rates and frequent relapses associated with conventional treatments suggest the involvement of underlying maladaptive behavioral patterns that share clinical and neurobiological substrates with substance use disorders, operationalized as Food Addiction (FA).

Objective: To review and analyze the neurobiological, neuroendocrine, and behavioral mechanisms underlying food addiction and the phenomenon of "food noise," evaluating their direct implication in the genesis, maintenance, and treatment resistance of obesity and diabesity.

Development and Mechanisms: This review examines the critical transition from homeostatic hunger (regulated by the hypothalamus) to hedonic hunger, governed by the mesocorticolimbic dopaminergic pathway. Chronic consumption of hyperpalatable ultra-processed foods functions as a supraphysiologic stimulus that induces massive dopamine release in the nucleus accumbens (NAc), driving an adaptive down-regulation of D2 receptors, hedonic tolerance, and a state of basal hypodopaminergia. This deficit weakens the top-down inhibitory control of the prefrontal cortex, impairing the capacity to modulate intense cravings. Additionally, functional neuroimaging studies confirm connectivity alterations within the reward and salience networks, displaying significant sex-dependent variations. Finally, we integrate the modulating role of peripheral signals (ghrelin, leptin, insulin, and incretins), the impact of gut microbiota via bacteriophages on neurotransmitter metabolism, and the concept of evolutionary mismatch.

Conclusions: Conceptualizing diabesity through the addiction paradigm dismantles the stigma of a lack of "willpower" and demands a shift in therapeutic approaches. Effective management of this condition requires integrated strategies combining behavioral psychotherapy (focused on anxiety regulation and mindful eating) alongside novel pharmacological tools (GLP-1/GIP receptor co-agonists), which are capable of mitigating food noise, restoring prefrontal executive function, and enabling the biological consolidation of sustainable healthy habits.