Thermogenic Gene Expression in Human Neck Adipose Tissue in Relation to Circulating and Local Thyroid Hormone Levels

Figures

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  Figure 1.. Thyroid status of the study patients at the time of the thyroid surgery. (A) Two patients with Graves’ disease on methimazole who also took Lugol's solution for 10 days before the surgery had thyroid function tests in the overt hypothyroid range at the time of the surgery (TSH 18.17 µIU/L [reference range 0.4-4.5 µIU/L], free T4 0.6 ng/dL [reference range 0.8-1.8 ng/dL], free T3 3.0 pg/mL [reference range 2.3-4.2 pg/mL]; TSH 18.48 µIU/L, free T4 0.4 ng/dL, free T3 2.2 pg/mL), respectively; 1 patient was hypothyroid for 5 weeks, whereas the second patient was euthyroid/hypothyroid for 4 weeks while taking methimazole before starting Lugol's solution before the thyroid surgery. (B) One patient with a hyperfunctioning thyroid nodule/Graves’ disease who was on methimazole and took Lugol's solution for 10 days before the surgery had thyroid function tests within normal range at the time of the surgery (TSH 0.77 µIU/L, free T4 0.8 ng/dL, free T3 2.8 pg/mL); the patient was euthyroid on methimazole for at least 2 months before surgery. (C) One euthyroid patient with benign thyroid nodules had only subcutaneous adipose tissue (no deep adipose tissue) removed during the surgery. (D) One…

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  Figure 2.. Differences between deep perithyroidal and subcutaneous (SC) neck adipose tissue in: (A) adipose tissue T3 concentration (per microgram of protein in tissue); (B) adipose tissue T4 concentration (per microgram of protein in tissue); (C) adipose tissue T3 concentration (per milligram of tissue); (D) adipose tissue T4 concentration (per milligram of tissue); (E) TSH receptor (TSHR) gene expression; (F) thyroid hormone receptor α (THRA) gene expression; (G) thyroid hormone receptor β (THRB) gene expression; (H) solute carrier family 16 member 2 (SLC16A2) gene expression coding for the thyroid hormone transporter monocarboxylate transporter 8 (MCT8); (I) solute carrier family 16 member 10 (SLC16A10) gene expression coding for the thyroid hormone transporter monocarboxylate transporter 10 (MCT10); (J) solute carrier family 6 member 8 (SLC6A8) gene expression coding for a membrane protein that transports creatine into and out of cells; (K) deiodinase 1 (DIO1) gene expression; (L) deiodinase 2 (DIO2) gene expression; (M) deiodinase 3 (DIO3) gene expression; (N) β-3 adrenergic receptor (ADRB3) gene expression; (O) uncoupling protein 1 (UCP1) gene expression; (P) PR domain-containing 16…

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  Figure 3.. Correlations between serum TSH, T4, and T3, and local adipose tissue T3 and T4 levels. (A) Serum TSH and serum free T4, (B) Serum TSH and serum free T3, (C) Serum free T4 and serum free T3, (D) Serum TSH and tissue T3, (E) Serum TSH and tissue T4, (F) Serum free T4 and tissue T4, (G) Serum free T3 and tissue T3. A P < .05 is considered statistically significant.

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  Figure 4.. Correlations of thermogenesis-related pathways with serum and local thyroid hormone levels in deep neck and subcutaneous adipose tissue. Fill reflects the sign of the normalized enrichment score (NES). A positive NES indicates pathway upregulation, and a negative NES indicates pathway downregulation.

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  Figure 5.. Enriched pathways correlated with serum free T4 concentration. (A) Normalized enrichment score of the top 5 correlated pathways in deep and subcutaneous neck adipose tissue samples. (B) Normalized enrichment score of thermogenic pathways. Fill reflects the sign of the normalized enrichment score (NES). A positive NES indicates pathway upregulation, and a negative NES indicates pathway downregulation. *FDR < 0.05.

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  Figure 6.. Enriched pathways correlated with serum free T3 concentration. (A) Normalized enrichment score of the top 5 correlated pathways in deep and subcutaneous neck adipose tissue samples. (B) Normalized enrichment score of thermogenic pathways. Fill reflects the sign of the normalized enrichment score (NES). A positive NES indicates pathway upregulation, and a negative NES indicates pathway downregulation. *FDR < 0.05.