You know there has been an explosion of new research about leptin. This new research has begun to shed light on leptin’s interplay with various systems in the body. So in this instalment, we are going to delve much deeper into leptin and thyroid gland. Specifically, we are going to discuss how leptin’s direct interaction with the thyroid promotes weight loss. However, keep in mind that in this instalment we are only going to be dealing with leptin’s direct effects on thyroid hormones.

Leptin and Thyroid

Much of leptin’s punch occurs because of downstream signals and various changes regulated by leptin’s interaction with the brain and nervous system. So keep that in mind as you read this article. Leptin’s powerful central effects cannot be denied. However to understand how it accomplishes some of this I have tried to ignore any systemic effects in this article.

Before we dive in and start discussing leptin’s profound effects on the thyroid system, let me first give a very brief review of the hypothalamus-pituitary-thyroid axis.

Thyrotropin-Releasing Hormone (TRH)

That wonderful little control centre in your brain, the hypothalamus, releases a protein called Thyrotropin-Releasing Hormone (TRH). TRH wanders over to the pituitary gland and causes it to release another hormone called Thyrotropin or Thyroid Stimulating Hormone, but for the remainder of this article, we will simply refer to it as TSH. TSH is then relayed to the thyroid gland where the thyroid gland secretes—you guessed it—thyroid hormone.

With that out of the way, we can now discuss leptin’s effects on the thyroid hormone control system. Before I do, however, I would like to caution the reader to pay extra close attention to this section and to read it very carefully. I have no idea why but for some reason leptin and the thyroid system have not been discussed in detail in any bodybuilding literature that I am aware of.

The reason that I advise you to pay close attention to this section is that, in my opinion, leptin is not some sideline player that has only a small effect on the thyroid. It is my contention that leptin is a key player in this system. It may even be the single most important factor governing thyroid hormone levels in healthy individuals.

Leptin’s Effects on the Hypothalamus

First, let us discuss leptin’s effects on the hypothalamus. When leptin initiates its signal cascade at the hypothalamus it increases TRH output (1). This increase in TRH should cause a concurrent increase in TSH at the pituitary; it should lead to higher levels of thyroid hormone in the blood stream. The literature confirms this as elevated leptin levels are associated with elevated thyroid hormone levels as well. But guess what: that not at all how it works. Now let’s dive deeper into this system to see why leptin is such a key player in determining thyroid hormone levels (2).

It is true that leptin causes TRH to be released from the hypothalamus. Where things get strange is leptin’s effects on the pituitary gland. As stated previously, one would think that increased TRH results in increased TSH. But this is not the case when one takes leptin’s role into account. In actuality, the higher the leptin levels are, the lower the level of TSH. This is confusing, I know; it is true, however (3).

Normally lower TSH means lower thyroid hormone levels—at least in the long run in healthy people. In the short term, however, TSH and thyroid hormone operate in a negative feedback loop. When thyroid hormone levels get high it causes TSH to go down. When TSH gets too low thyroid hormone levels to drop and TSH goes back up. Thus it was thought that TRH is really the main control since TSH and thyroid hormone levels are constantly in oppositional flux.

Leptin throws a monkey wrench into this supposition, however. Specifically, leptin is directly suppressive to TSH release in the pituitary. In fact, it has even been hypothesized that since the pituitary gland creates leptin of its own this is one avenue through which it lowers its own TSH output.

Leptin’s Effects on the Thyroid Gland

Leptin’s effects on the thyroid gland itself are also very interesting. When leptin signals at the thyroid gland it causes thyroid hormone to be released (4). As you can see this is a pretty complicated relationship. To reiterate: Leptin is positive at the thyroid gland and hypothalamus but negative at the pituitary. This strange relationship is why leptin is such a key player in the control of thyroid hormone levels.

Essentially, leptin somewhat overrides the ‘normal’ control system, controlling and in many ways ultimately determining thyroid hormone levels. To shed some light on this paradox, lets stop looking at in vitro research and examine some in vivo studies to see how this really works.

Normally when in caloric restriction, leptin levels and thyroid hormone levels drop. Supplemental leptin administration, given at a replacement dose, brings thyroid hormone levels back within a normal range (5). In a very interesting study rats were starved at 10% below there maintenance calorie levels and monitored for an extended period. During this time—as you would expect—leptin, T3, and T4 levels were all reduced. The researchers then administered the rats with just enough leptin to get them back to their previous pre-dieting levels. As you would expect, thyroid hormone levels returned to normal.

Effect of Supplemental Leptin

What is interesting is that in a related study, researchers monitored rats that were given supplemental leptin. In these rats TSH was remarkably reduced yet T3/T4 levels were significantly elevated (22). The only viable explanation is that leptin short-circuits the normal negative feedback-loop between the pituitary and the thyroid gland. Essentially, leptin takes control of the thyroid gland and determines the amount of thyroid hormone released.

The Link Between TSH and Leptin

The link between TSH and leptin is even stronger than one might imagine. TSH not only signals the thyroid gland to make thyroid hormone, but it also signals adipose tissue to make leptin (6). It is very potent I might add. In one study researchers took human adipose tissue from elective surgery patients and incubated it with TSH. TSH powerfully stimulated leptin release comparable to that seen by glucose and insulin.

Now, that probably comes as a surprise. It appears leptin and TSH operate in a negative feedback loop similar to TSH and thyroid hormone. There is very strong evidence to support this supposition. TSH and leptin blood levels follow the exact same diurnal rhythm. In fact, they are so synchronous that their peak blood levels coincide. So it would seem that this negative feedback loop between the two is very efficient and quite powerful (7).

So at this point, I think it’s safe to say that leptin is very important for the regulation of the hypothalamus-pituitary-thyroid axis. Furthermore, it provides some direct insight as to why leptin levels don’t plummet to next to anything when one’s calories are reduced. You see in the absence of the “feed signal,” TSH output increases due to the drop in thyroid hormone, which in turn serves as a very potent signal to the adipose to secrete leptin.

I know this was a lot of information to take in at once. I suggest you reread it again as, in your humble author’s opinion, the link between leptin and thyroid hormones cannot be overstated.

Concluding Leptin and Thyroid Hormones

Well, that’s all for now. Take some time and ponder the ramifications of all of this. In the next instalment of this series, we will examine leptin’s effects on various parts of the brain and nervous system, and how it relates to fat loss. This is where things will really start to become interesting, as much of leptin’s power does not come from interacting with various body tissues.

Leptin’s primary source of influence comes from its interaction with the brain and the central nervous system. Leptin’s systemic indirect effects are vitally important to its function. These indirect effects are the reason you get the munchies and the reason you can barely get your ass out of bed in the morning while dieting.

Refernces for 'Leptin and Thyroid'

(1) J Clin Invest 2001 Jan;107(1):111-20 Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN; PMID: 11134186

(2) Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab. 2002 May;87(5):2391-4. doi: 10.1210/jcem.87.5.8628. PMID: 11994393.

(3) Ortiga-Carvalho TM, Oliveira KJ, Soares BA, Pazos-Moura CC. The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies. J Endocrinol. 2002 Jul;174(1):121-5. doi: 10.1677/joe.0.1740121. PMID: 12098670.

(4) Nowak KW, Kaczmarek P, Mackowiak P, Ziolkowska A, Albertin G, Ginda WJ, Trejter M, Nussdorfer GG, Malendowicz LK. Rat thyroid gland expresses the long form of leptin receptors, and leptin stimulates the function of the gland in euthyroid non-fasted animals. Int J Mol Med. 2002 Jan;9(1):31-4. PMID: 11744992.

(5) Clin Endocrinol Metab 2002 May;87(5):2391 Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL. PMID: 16322796

(6) Menendez C, Baldelli R, Camiña JP, Escudero B, Peino R, Dieguez C, Casanueva FF. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003 Jan;176(1):7-12. doi: 10.1677/joe.0.1760007. PMID: 12525244.

(7) J Clin Endocrinol Metab 2001 Jul;86(7):3284 Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. Harris M, Aschkenasi C, Elias CF, Chandrankunnel A, Nillni EA, Bjoorbaek C, Elmquist JK, Flier JS, Hollenberg AN. PMID: 20074584.