Iodine Deficiency Increases Fat Contribution to Energy Expenditure in Male Mice.

More than a billion people worldwide are at risk of iodine deficiency (ID), with well-known consequences for development of the central nervous system. Furthermore, ID has also been associated with dyslipidemia and obesity in humans. To further understand the metabolic consequences of ID, here we kept 8-week-old C57/Bl6 mice at thermoneutrality (~28°C) while feeding them on a low iodine diet (LID). When compared with mice kept on control diet (LID + 0.71 μg/g iodine), the LID mice exhibited marked reduction in T4 and elevated plasma TSH, without changes in plasma T3 levels. LID mice grew normally, and had normal oxygen consumption, ambulatory activity, and heart expression of T3-responsive gene, confirming systemic euthyroidism. However, LID mice exhibited ~5% lower respiratory quotient (RQ), which reflected a ~2.3-fold higher contribution of fat to energy expenditure. LID mice also presented increased circulating levels of nonesterified fatty acids, ~60% smaller fat depots, and increased hepatic glycogen content, all indicative of accelerated lipolysis. LID mice responded much less to forced mobilization of energy substrates (50% food restriction for 3 days or starvation during 36 hours) because of limited size of the adipose depots. A 4-day treatment with T4 restored plasma T4 and TSH levels in LID mice and normalized RQ. We conclude that ID accelerates lipolysis and fatty acid oxidation, without affecting systemic thyroid hormone signaling. It is conceivable that the elevated plasma TSH levels trigger these changes by directly activating lipolysis in the adipose tissues.