Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical
Plastic materials are ubiquitous, leading to constant human exposure to plastic additives such as plasticizers. There is growing evidence that plasticizers may contribute to obesity due to their disruptive effects on metabolism. Alternatives like diisononylcyclohexane-1,2-dicarboxylate (DINCH) are r...
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Elsevier
2025-02-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412025000571 |
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| author | Sontje Krupka Alix Sarah Aldehoff Cornelius Goerdeler Beatrice Engelmann Ulrike Rolle-Kampczyk Kristin Schubert Nora Klöting Martin von Bergen Matthias Blüher |
| author_facet | Sontje Krupka Alix Sarah Aldehoff Cornelius Goerdeler Beatrice Engelmann Ulrike Rolle-Kampczyk Kristin Schubert Nora Klöting Martin von Bergen Matthias Blüher |
| author_sort | Sontje Krupka |
| collection | DOAJ |
| description | Plastic materials are ubiquitous, leading to constant human exposure to plastic additives such as plasticizers. There is growing evidence that plasticizers may contribute to obesity due to their disruptive effects on metabolism. Alternatives like diisononylcyclohexane-1,2-dicarboxylate (DINCH) are replacing traditional phthalates such as di-(2-ethylhexyl) phthalate (DEHP), which are now banned due to their proven harmful health effects. While DINCH is considered a safer alternative to DEHP and no adipogenic effects have been demonstrated in in vivo studies, recent research suggests that the primary metabolite, monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH), promotes adipocyte differentiation and dysfunction in vitro. However, metabolic and molecular effects are not fully understood in vivo.Here, we performed a comprehensive in vivo analysis using C57BL/6N mice to investigate the effects of DINCH on adipose tissue physiology and function. Mice were exposed to two doses of DINCH for 16 weeks, followed by a 10-week recovery period. Tissue analysis confirmed the presence of DINCH and MINCH in liver and adipose tissue after treatment and recovery. After the recovery period, elevated DINCH concentrations in adipose tissue depots indicated possible bioaccumulation. Although no changes were observed in body composition and energy expenditure, sex-specific metabolic effects were identified. Female mice exhibited impaired whole-body insulin sensitivity and higher triglyceride levels, while male mice showed an altered insulin/C-peptide ratio and elevated cholesterol, HDL, and LDL levels. Proteomic profiling of serum, adipose and liver tissues revealed changes in pathways related to central energy metabolism and immune response, highlighting the systemic impact of DINCH, potentially on inflammatory processes. Most effects of DINCH, such as changes in insulin response and serum lipid levels, were diminished after the recovery period.Despite many findings consistent with the existing literature suggesting DINCH as a safer DEHP substitute, the observed sex-specific effects on insulin sensitivity, lipid metabolism and inflammatory processes, as well as potential bioaccumulation and long-term metabolic effects of DINCH exposure warrant careful consideration in further risk assessment. |
| format | Article |
| id | doaj-art-66cd51069f684864b0a599f52b8580d7 |
| institution | Kabale University |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj-art-66cd51069f684864b0a599f52b8580d72025-01-31T05:10:03ZengElsevierEnvironment International0160-41202025-02-01196109306Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemicalSontje Krupka0Alix Sarah Aldehoff1Cornelius Goerdeler2Beatrice Engelmann3Ulrike Rolle-Kampczyk4Kristin Schubert5Nora Klöting6Martin von Bergen7Matthias Blüher8Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Centre München at the University of Leipzig Germany; Department of Endocrinology Nephrology Rheumatology University Hospital Leipzig Medical Research Center Leipzig GermanyDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig GermanyDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig GermanyDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig GermanyDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig GermanyDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig Germany; Corresponding authors.Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Centre München at the University of Leipzig Germany; Corresponding authors.Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ) Leipzig Germany; Institute of Biochemistry Faculty of Biosciences, Pharmacy and Psychology Leipzig University Leipzig Germany; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig Leipzig Germany; Corresponding authors.Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Centre München at the University of Leipzig Germany; Department of Endocrinology Nephrology Rheumatology University Hospital Leipzig Medical Research Center Leipzig GermanyPlastic materials are ubiquitous, leading to constant human exposure to plastic additives such as plasticizers. There is growing evidence that plasticizers may contribute to obesity due to their disruptive effects on metabolism. Alternatives like diisononylcyclohexane-1,2-dicarboxylate (DINCH) are replacing traditional phthalates such as di-(2-ethylhexyl) phthalate (DEHP), which are now banned due to their proven harmful health effects. While DINCH is considered a safer alternative to DEHP and no adipogenic effects have been demonstrated in in vivo studies, recent research suggests that the primary metabolite, monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH), promotes adipocyte differentiation and dysfunction in vitro. However, metabolic and molecular effects are not fully understood in vivo.Here, we performed a comprehensive in vivo analysis using C57BL/6N mice to investigate the effects of DINCH on adipose tissue physiology and function. Mice were exposed to two doses of DINCH for 16 weeks, followed by a 10-week recovery period. Tissue analysis confirmed the presence of DINCH and MINCH in liver and adipose tissue after treatment and recovery. After the recovery period, elevated DINCH concentrations in adipose tissue depots indicated possible bioaccumulation. Although no changes were observed in body composition and energy expenditure, sex-specific metabolic effects were identified. Female mice exhibited impaired whole-body insulin sensitivity and higher triglyceride levels, while male mice showed an altered insulin/C-peptide ratio and elevated cholesterol, HDL, and LDL levels. Proteomic profiling of serum, adipose and liver tissues revealed changes in pathways related to central energy metabolism and immune response, highlighting the systemic impact of DINCH, potentially on inflammatory processes. Most effects of DINCH, such as changes in insulin response and serum lipid levels, were diminished after the recovery period.Despite many findings consistent with the existing literature suggesting DINCH as a safer DEHP substitute, the observed sex-specific effects on insulin sensitivity, lipid metabolism and inflammatory processes, as well as potential bioaccumulation and long-term metabolic effects of DINCH exposure warrant careful consideration in further risk assessment.http://www.sciencedirect.com/science/article/pii/S0160412025000571DINCHMINCHMetabolic disruptionObesityAdipose tissue |
| spellingShingle | Sontje Krupka Alix Sarah Aldehoff Cornelius Goerdeler Beatrice Engelmann Ulrike Rolle-Kampczyk Kristin Schubert Nora Klöting Martin von Bergen Matthias Blüher Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical Environment International DINCH MINCH Metabolic disruption Obesity Adipose tissue |
| title | Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical |
| title_full | Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical |
| title_fullStr | Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical |
| title_full_unstemmed | Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical |
| title_short | Metabolic and molecular Characterization, following dietary exposure to DINCH, Reveals new Implications for its role as a Metabolism-Disrupting chemical |
| title_sort | metabolic and molecular characterization following dietary exposure to dinch reveals new implications for its role as a metabolism disrupting chemical |
| topic | DINCH MINCH Metabolic disruption Obesity Adipose tissue |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025000571 |
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