Reduction in T-Cell Mitochondrial Respiratory Capacity After Reaching a Weight Loss Plateau

Experiencing an involuntary weight loss plateau is common after behavioral weight loss. During such periods, sustained negative energy balance activates counterregulatory mechanisms that restore energy balance and may slow further weight loss. However, the cellular bioenergetic changes occurring specifically during a spontaneous weight loss plateau have not been investigated. We studied mitochondrial respiratory capacity in peripheral mononuclear cell populations from participants with obesity, both before and after an intensive lifestyle intervention (ILI). Body weight was tracked continuously over 18 months using a remote electronic scale, enabling retrospective categorization of outcome measures by weight loss phases: active weight loss (aWL), plateau (PL), or regain (RG). Differences in mitochondrial respiration were observed in T cells but not in monocytes across these phases. During aWL, mitochondrial respiratory capacity was similar to pre-ILI; however, basal, ATP-linked, maximal, and spare respiratory capacity were significantly lower during the PL and RG phases. In addition, ATP-linked respiration was lower in the PL and RG, despite higher mitochondrial citrate synthase activity in the PL relative to pre-ILI. These results indicate that T-cell bioenergetics may be responsive to shifts in energy balance during weight reduction. The novel phase-specific classification used in this study uncovers dynamic bioenergetic adaptations that may contribute to a weight loss plateau.

Weight loss is a dynamic process, characterized by transitions between active weight loss, plateau, and regain, yet underlying metabolic features across these phases remain poorly defined. This study tested whether mitochondrial bioenergetics in peripheral mononuclear cells differ in humans across weight loss phases during behavioral weight loss. Mitochondrial respiratory capacity of T cells is significantly reduced during plateau and regain phases, despite an increase in mitochondrial content. Phase-based classification of weight change reveals bioenergetic differences in T cells that are associated with transitions in energy balance within the weight-reduced state.