Energy Expenditure in Obesity: Relationship with NNMT, Polyamine Cycle, and Response to Caloric Restriction

Objective: Resting energy expenditure (REE) is an important factor for weight regulation. Factors associated with REE are incompletely defined. N1-Methylnicotinamide (MNA-1) and N1,N12-diacetylspermine have emerged as new factors for REE. To study factors associated with REE and the response to energy restriction. Design: A prospective study examining the response to a hypocaloric restriction diet. 223 healthy individuals in two groups: 115 with normal weight and 108 with obesity. We collected anthropometry, caloric intake, sleep duration, and physical activity. REE was measured by indirect calorimetry. Plasma MNA-1 and N1,N12-diacetylspermine concentrations were measured by LC-MS. Insulin, leptin, meteorin-like protein and acylated-ghrelin were quantified by ELISA. The group with obesity received a hypocaloric diet for 7 weeks and measurements were repeated at the end of intervention. Results: Obese subjects reported less sleep duration, and showed higher REE, and MNA-1 but lower N1,N12-diacetylspermine levels. After diet, obese subjects lost 4.4 kg. REE diminished and N1,N12-diacetylspermine levels increased. The factors associated with REE were positively BMI, caloric intake, creatinine, and physical activity and negatively leptin and age. REE is strongly dependent on body size, muscular mass and function, and body fat. In obesity, MNA-1 is increased and N1,N12-diacetylspermine decreased, changes reversed with caloric restriction, suggesting a more direct dependence with metabolic balance than with body composition. Conclusions: This study confirms that obesity is associated with less time of sleep, and increased REE. REE was associated with BMI, muscular activity, and with age. MNA-1 seems to be associated with fat metabolism. Diacetylspermine increases with caloric restriction. Funding: Carolina Marin-Aragon was a recipient of a Post-graduate fellowship from CONACYT. This work was supported by the grant CB2014-242065M from Consejo Nacional de Ciencia y Tecnologia (CONACYT, to JMM), and by the grant 177/2016 from University of Guanajuato (Convocatoria Institucional para Fortalecer la Excelencia Academica (CIFOREA), to NF-V). Declaration of Interest: The authors do not have competing financial interests to declare. Ethical Approval: This study was approved by the Institutional Bioethics Committee (No. 017/2015). Its nature and possible risks were explained to all participants, and those who agreed to participate provided informed consent.