Proceedings of The Physiological Society

Experimental Models (Exeter, UK) (2018) Proc Physiol Soc 40, C08

Oral Communications

Hypothyroidism induces hyperplasia of unilocular adipocytes in perirenal adipose tissue of the ovine fetus

S. Harris2,1, M. J. De Blasio3, F. Wooding3, D. Blache4, A. Fowden3, A. Forhead2,3

1. OCDEM, University of Oxford, Oxford, Oxon, United Kingdom. 2. Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, United Kingdom. 3. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom. 4. School of Animal Biology, University of Western Australia, Crawley, Western Australia, Australia.

Thyroid hormones are important regulators of fetal growth, although their mechanism of action remains unclear. In the sheep fetus, thyroid hormone deficiency increases plasma insulin and leptin concentrations (1). This study investigated the effects of hypothyroidism on perirenal adipose tissue (PAT) development and adipose insulin signalling pathways in fetal sheep. All procedures were performed under the UK Animals (Scientific Procedures) Act 1986. In 10 twin-bearing pregnant ewes at 105-110 days of gestation (d; term~145d) and under general anaesthesia (1.5% isoflurane in O2/N2O), one fetus was thyroidectomised (TX), while the other was sham-operated. At 143d, fetuses were delivered by Caesarean section under general anaesthesia (20 mg kg−1 maternal body weight sodium pentobarbitone i.v.). After maternal and fetal euthanasia (200 mg kg−1 sodium pentobarbitone i.v.), PAT was collected, weighed, and frozen or processed for histology and stereological assessment. Protein and mRNA content were determined by Western blotting and qRT-PCR. Data (mean±SEM) were assessed by Student's t-test. Absolute and relative PAT mass was increased in TX fetuses compared to sham fetuses (absolute: sham 10.9±1.1g, TX 14.7±1.1g, P<0.05; relative: sham 3.1±0.3g/kg, TX 4.8±0.4g/kg P<0.05). This was due to a 2-fold increase in absolute and relative mass of unilocular (white) adipocytes (absolute: sham 3.3±0.6g, TX 7.2±0.7g, P<0.001; relative: sham 1.1±0.2g/kg, TX 2.3±0.3g/kg, P<0.05), with no change in the mass of multilocular (brown) adipocytes. Relative unilocular adipocyte mass correlated positively with plasma insulin (r=0.76, P<0.001) and leptin (r=0.64, P<0.002). Unilocular adipocyte perimeter was unaffected by TX which indicated that thyroid hormone deficiency in utero induced hyperplasia rather than hypertrophy of unilocular adipocytes. In PAT from TX fetuses, increases were observed in protein levels of proliferating cell nuclear antigen, the insulin-sensitive glucose transporter-4 and phosphorylated S6-kinase, and in mRNA and protein levels of the differentiation marker, peroxisome proliferator-activated receptor-γ (P<0.05). In the ovine fetus, development of unilocular adipocyte mass in PAT is sensitive to changes in thyroid hormones, which may be related, in part, to altered insulin concentrations in utero. These findings have implications for the control of adipose function and leptin secretion before and after birth

Where applicable, experiments conform with Society ethical requirements