Tributyltin differentially promotes development of a phenotypically distinct adipocyte

Abstract

ObjectiveEnvironmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being pro-adipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known.MethodsThe co-stimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose.ResultsTBT enhanced expression of the adipocyte marker C/EBPα with co-exposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of co-treatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake.ConclusionsTBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis.

Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero

“…About 10 years ago, it was first proposed that some EDCs are putative obesogens, with properties that alter the control of adipogenesis and energy balance (Grün and Blumberg, 2006) and lead to increased body weight. Obesogenic EDCs include tributyltin, tolyfluanid, and DES (Grün and Blumberg, 2006; Newbold et al, 2007; Regnier et al, 2015). A body burden of EDCs is also predictive of metabolic disorders and obesity in human populations (Lee et al, 2011).…”

Transgenerational effects of obesogens

“…Considering how many chemicals increase the commitment or differentiation of adipocytes, it is reasonable to ask whether the adipocytes produced are normal and fully functional . Such studies were prompted by the studies of Sargis and colleagues who investigated the effects of TBT vs the pharmaceutical PPARγ activator, troglitazone on the differentiation and function of 3T3‐L1 pre‐adipocytes, in vitro . TBT‐induced adipocytes produced lower levels of adiponectin and CEBPα mRNA and protein than did troglitazone‐induced adipocytes.…”

“…TBT‐induced adipocytes produced lower levels of adiponectin and CEBPα mRNA and protein than did troglitazone‐induced adipocytes. The TBT‐induced adipocytes displayed reduced GLUT4 expression but normal glucose uptake and they inferred that TBT had produced “unhealthy” adipocytes . White adipocytes play an important role in metabolic health by removing glucose from the circulation when stimulated by insulin .…”

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

“…Thereafter, a growing number of studies showed that exposure to TBTCl resulted in obesity, and hepatic steatosis in rodents . Moreover, one recent study in vitro showed that TBT reduced adiponectin expression . Adiponectin can counteract multiple manifestations of MS and serve as a valuable biomarker for MS .…”