1645-P: Metabolic and Adipogenic Effects of Di(isononyl) Cyclohexane-1,2-dicarboxylate (DINCH) In Vivo

As a substitute for phthalate plasticizers, DINCH holds significance. Human studies indicate that lipophilic xenobiotics, including DINCH, accumulate in adipose tissue, potentially disrupting adipocyte biology and contributing to metabolic disturbances like insulin resistance and obesity. In vitro experiments demonstrate the activation of PPARg in adipocytes by DINCH. To provide further clarification on the effects of DINCH, we conducted a feeding study. A total of 144 C57BL/6NTac mice (N=144; females N=72, males N=72) were randomly assigned into four groups, each receiving distinct dietary interventions: standard chow, high-fat diet (HFD), and HFD supplemented with 4,500 ppm and 15,000 ppm DINCH. Throughout the 16-week study, animals had unrestricted access to their designated diets. To explore potential washout effects, 80 animals shifted to a standard diet for an additional 10 weeks following the initial intervention. The study included routine evaluations of body weight, blood glucose, insulin tolerance, and body composition (fat mass/lean mass). At the study's conclusion, metabolic chamber analysis assessed energy metabolism, and tissues were scrutinized at both molecular and histological levels post-euthanization. In contrast to expectations, mice fed the HFD-DINCH diet exhibited lower body weights than the standard HFD group, with minimal changes in fat and lean mass distribution. The DINCH-fed mice demonstrated increased insulin resistance and dyslipidemia, which were reversible during the washout phase. These results suggest a need to reevaluate the presumed effects of DINCH on adipocyte differentiation and lipid accumulation. They provide new insights into the interplay between DINCH exposure and metabolic responses in mice.<u></u>