Effects of an environmentally relevant mixture of organochlorine pesticide compounds on adipogenesis and adipocyte function in an immortalized human adipocyte model

Abstract

Exposure to persistent organic pollutants (POPs), including organochlorine (OC) pesticide POPs, has been associated with the increased prevalence of obesity and type 2 diabetes. However, the underlying mechanisms through which exposure to these compounds may promote obesity and metabolic dysfunction remain an area of active investigation. To this end, the concentration dependent effects of an environmentally relevant mixture of OC pesticide POPs on adipocyte function was explored utilizing a translationally relevant immortalized human subcutaneous preadipocyte/adipocyte model. Briefly, immortalized human preadipocytes/adipocytes were exposed to a mixture of dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, and oxychlordane (DTO) then key indices of preadipocyte/adipocyte function were assessed. Exposure to DTO did not alter adipogenesis. However, in mature adipocytes, exposure to DTO slightly increased fatty acid uptake whereas isoproterenol stimulated lipolysis, basal and insulin stimulated glucose uptake, mitochondrial membrane potential, and cellular ATP levels were all significantly decreased. DTO significantly increased Staphylococcus aureus infection induced increases in expression of pro-inflammatory cytokines IL-6, IL-1β, and Mcp-1 as well as the adipokine resistin. Taken together, the present data demonstrated exposure to an environmentally relevant mixture of OC pesticide compounds can alter mature adipocyte function in a translationally relevant human adipocyte model which further supports the adipose tissue as an effector site of OC pesticide POPs action.