Pre-eclampsia (PE) is a disorder of human pregnancy, which is defined as new onset hypertension with proteinuria. In recent years, a role for adipose tissue (AT) dysfunction has emerged in PE pathology. Women with PE display exaggerated insulin resistance in subcutaneous AT (SAT) at third trimester compared to normotensive (NT) controls, without evidence of hypertrophy¹. This may indicate a reduced capacity in PE to store gestationally-acquired fat within AT. We hypothesised that increased AT fibrosis in PE, defined as excessive accumulation of extracellular matrix components including collagens, could limit healthy AT expansion in PE.

Non-labouring pregnant women in the third trimester with PE, as defined by ISSHP guidelines, and age- and BMI-matched NT controls undergoing elective C-section at the Glasgow Royal Infirmary were consented for SAT and visceral AT (VAT) biopsy collections. Ethical approval was granted from the Glasgow Royal Infirmary Local Research Ethics Committee (06/S0704/14). Adipocyte diameter was assessed by manual microscopic sizing of a minimum of 100 adipocytes. Fibrosis was quantified in paraffin embedded AT sections using picrosirius red staining (PE n=11, NT n=6). Acquired images of stained whole tissue sections were converted to 8-bit images, background area subtracted and total red staining of collagen fibres (%) measured in ImageJ. Taqman qRT-PCR was used to measure mRNA expression relative to the endogenous control PPIA in whole AT (n=6 per group) and isolated adipocytes (n=9 per group). Data were analysed using repeated measures mixed-effects models of PE status (NT or PE) and AT depot (SAT or VAT) and their interaction; mean ± SD reported.

There was no difference in mean adipocyte diameter between PE (SAT: 113.6 ± 9.6µm, VAT: 90.6 ± 10.6µm) and NT (SAT: 111.7 ± 7.9µm, VAT: 88.2 ± 8.3µm) (P_{PE status}=0.53, P_{AT depot}<0.001, P_interaction=0.90). There was no difference in tissue collagen content between NT and PE (P_{PE status}=0.56, P_{AT depot}=0.55, P_interaction=0.39). Whole AT COL6A3 (P_{PE status}=0.41, P_{AT depot}=0.005, P_interaction=0.51), COL1A1 (P_{PE status}=0.76, P_{AT depot}=0.16, P_interaction=0.21) and COL4A1 (P_{PE status}=0.17, P_{AT depot}<0.001, P_interaction=0.20) mRNA expression was not different between PE and NT.  Interestingly, whole AT mRNA expression of TGFB1 was higher in PE compared to NT (P_{PE status}=0.012, P_{AT depot}=0.039, P_interaction=0.73). Isolated adipocyte COL4A1 mRNA expression was higher in PE compared to NT (P_{PE status}=0.044, P_{AT depot}<0.001, P_interaction=0.64). Adipocyte TGFB1 expression did not differ between PE and NT (P_{PE status}=0.91, P_{AT depot}=0.001, P_interaction=0.48).

In conclusion, while there was no effect of PE on AT fibrosis, higher adipocyte expression of COL4A1, a key basement membrane component was observed. This has also been seen in adipocytes from obese individuals² suggesting similar localised restriction of adipocyte hypertrophy in PE which may contribute to impaired AT expansion. Higher whole AT, but not adipocyte, TGFB1 expression (a regulator of COL4A1 transcription) indicates that TGFβ is produced by stromal vascular cells. Understanding the relationship between TGFβ and adipocyte collagen type IV may shed light on defective adipocyte differentiation in PE pregnancies.