FIG. 9.

Schematic representation of the suggested hypothesis. During periods of a positive-energy balance, white adipose tissue expands to meet the need for extra triglyceride storage. As a consequence, adipose tissue becomes hypoxic, thereby activating the transcription factor HIF1α. HIF1α in turn activates a host of genes involved in several physiological responses. Here, we demonstrate that this HIF1α activation initiates a fibrotic response and causes insulin resistance in white adipose tissue. Furthermore, we show that HIF1 induces the collagen cross-linker LOX, which plays a crucial part in this process. Finally, we hypothesize that HIF1-induced fibrosis can be the initiating factor for monocyte infiltration and inflammation.