Insulin resistance is associated with oxidative and endoplasmic reticulum (ER) stress, the accumulation of oxidatively damaged molecules, dysfunctional mitochondria, and protein aggregates. There are two major degradative pathways in cells to remove dysfunctional cellular components: the ubiquitin-proteasome system and autophagy. We hypothesised that in insulin resistant adipose tissue these degradative pathways are downregulated. This may increase susceptibility of cells to environment stress and be a causal factor leading to insulin resistance.  To address this, we determined autophagic activity (LC3-II) and ubiquitin-proteasome system activity in insulin resistant adipose.  We used two models of insulin resistance: 3T3-L1 adipocytes treated with 10nM insulin for 24h and mice fed a high fat diet (HFD) for 7 days. Insulin resistance was defined as reduced insulin stimulated glucose uptake in adipocytes, and impaired glucose tolerance in mice. In 3T3-L1 adipocytes exposed to short term hyperinsulinemia, despite impaired glucose uptake insulin mediated inhibition of autophagy is unaffected. Therefore it is likely that adipocytes exposed to hyperinsulinemia have reduced autophagy.  We next investigated a 7d HFD fed mice injected with 1U/kg insulin. Ubiquitin levels were reduced after 60 min in chow fed mice, indicating reduced ubiquitin-proteasome activity in response to insulin, whereas in HFD mice proteasome activity remained elevated with no corresponding decrease in total ubiquitin. HFD mice also exhibited increased autophagy. However, in contrast to that observed in adipocytes in vitro we were unable to observe any insulin-mediated suppression of autophagy in vivo in either chow or HFD animals despite robust phosphorylation of components of insulin signalling cascade (AKT, AS160 and PRAS40). Collectively, these data indicate that high fat diet leads to a defect in the regulation of proteasomal activity in adipose tissue indicating that insulin resistance is associated with impaired proteostasis.