Experimental Overweight Impairs Mitochodrial Brown Adipose Tissue Bioenergetics: Positive Effect After Serotonin Modulation

Infant overweight/obesity has achieved epidemiologic proportions worldwide and several metabolic dysfunctions are present in such condition. Brown adipose tissue (BAT) plays a critical role in thermogenesis and metabolic efficiency through mitochondrial function and recruitment of their mitochondrial uncoupling protein (UCP1). Besides that, some hormones as leptin also regulates energy metabolism by peripheral action in BAT. Interesting, early modulation of central serotonergic system with SSRI (Fx) can induce higher metabolic activity in BAT; even though the effects of Fx exposure later in life in experimental overweight/obese model was never studied. To study these effects, seventy‐two hours after delivery, puppies were randomly assigned into two groups: Normofed (nine pups/mother; n=9) or Overfed (three pups/mother; n=9). SSRI (Fx, 10mg/kg b.w.) or vehicle solution (NaCl 0.9%) administration was carried out from 39 th through 59 th day of age, according to the groups: Normofed + Vehicle (NV), Normofed + Fx (NF), Overfed + Vehicle (OV) and Overfed + Fx (OF). At 60 days of age UCP 1 protein expression, mitochondrial oxygen consumption‐MOC (in the presence or absence of the UCP inhibitor GDP) and ROS production, lipid peroxidation, protein oxidation, GSH and GSSG content and leptin gene expression were evaluated in the interscapular BAT (iBAT). Fx increased UCP 1 expression only in NF group (p=0.0076). Related to MOC in the absence of GDP, the basal state increased in OF group (p=0.0366). With GDP addition, both FLX groups increased MOC compared to their controls (NF: p=0.0003 and OF: p=0.050). In the uncoupling state without GDP, both groups had a higher MOC compared to their controls (NF: p=0.0316 and OF: p=0.0242) and presented superior MOC with GDP addition (NF: p<0.0001 and OF: p=0.0034). ROS production increased in NF group (p=0.0010) and in OV group (p=0.0143) and decreased in OF group (p=0.0036). Lipid peroxidation was higher in NF group (p=0.0177) and OV group (p=0.0001) and lower in OF group (p=0.0418). Protein oxidation increased in NF group (p=0.0072) and OV group (p=0.0247). GSSG content increased in NF group (p<0.0001) and decreased in OF group (p<0.0001). Redox state (GSH/GSSG) decreased in NF group (p=0.0092) and increased in OF group (p=0.0031). Leptin gene expression decreased in NF group (p=0.004) and increased in OF group (p=0.0434). Taken together our data suggest that Fx administration in early adult life was detrimental for mitochondrial oxidative balance in normofed conditions; on the other hand in overfed rats pharmacological intervention shows mitochondrial and oxidative improvements in iBAT and readjustment of peripheral metabolic efficiency. Support or Funding Information CAPES, CNPq and FACEPE This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .