3,5 is possibly suppressive, both have been shown to do nothing for BMR en vivo. I guess if you have hyperthyroidism it could be of some use.
Here:
3,5-Diiodo-L-thyronine (T2) & Fat Loss
3,5-Diiodo-L-thyronine (T2) is a putative T3 analog that, in at least one small human study, showed promise as a safe, effective fat-loss aid. Much of the research on T2 comes from the same guys in Italy so there are some legit questions about how reliable it is but there is also a good deal of rat research from other sources that appear to bolster the claims about T2's effects in humans.
First the tantalizing human study:
J Biol Regul Homeost Agents. 2011 Oct-Dec;25(4):655-60.
3,5-diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects.
Antonelli A, Fallahi P, Ferrari SM, Di Domenicantonio A, Moreno M, Lanni A, Goglia F.
Source
Department of Internal Medicine, University of Pisa, Pisa, Italy.
[email protected]
Abstract
Recently, it was demonstrated that 3,5-diiodo-L-thyronine (T2) stimulates the resting metabolic rate (RMR), and reduces body-weight gain of rats receiving a high-fat diet.
The aim of this study is to examine the effects of chronic T2 administration on basal metabolic rate and body weight in humans. Two euthyroid subjects volunteered to undergo T2 administration. Body weight, body mass index, blood pressure, heart rate, electrocardiogram, thyroid and liver ultrasonography, glycemia, total cholesterol, triglycerides, free T3 (FT3), free T4 (FT4), T2, thyroid stimulating hormone (TSH) and RMR were evaluated at baseline and at the end of treatment. RMR increased significantly in each subject.
After continuing the T2 treatment for a further 3 weeks (at 300 mcg/day), body weight was reduced significantly (p<0.05) (about 4 percent), while the serum levels of FT3, FT4 and TSH, were unchanged. No side effects were observed at the cardiac level in either subject. No significant change was observed in the same subjects taking placebo.
PMID: 22217997
Pretty cool. And the murine model to support the human study results:
FASEB J. 2005 Sep;19(11):1552-4. Epub 2005 Jul 12.
3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats.
Lanni A, Moreno M, Lombardi A, de Lange P, Silvestri E, Ragni M, Farina P, Baccari GC, Fallahi P, Antonelli A, Goglia F.
Source
Dipartimento di Scienze della Vita, Seconda Università di Napoli, Caserta, Italy.
[email protected]
Abstract
The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat reduction, but the concomitant induction of a thyrotoxic state has greatly limited their use. Recent evidence suggests that 3,5-diiodo-L-thyronine (T2), a naturally occurring iodothyronine, stimulates metabolic rate via mechanisms involving the mitochondrial apparatus. We examined whether this effect would result in reduced energy storage. Here, we show that T2 administration to rats receiving a high-fat diet (HFD) reduces both adiposity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, appoximately 50% less fat mass, a complete disappearance of fat from the liver, and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively). Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T2 administration. The biochemical mechanism underlying the effects of T2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling. If the results hold true for humans, pharmacological administration of T2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T2 on a longer time scale as well as do not show that T2 acts in the same way in humans.
PMID: 16014396
FFT
So it appears to potently stimulate hepatic fat oxidation...sounds like it might pair well with AAS that induce reverse cholesterol transport bringing fat from adipose tissue to the liver...
More Italian research indicating that T2 may be a metabolite of T3 in vivo and is partially responsible for T3's effects on RMR.
Endocrinology. 2002 Feb;143(2):504-10.
Are the effects of T3 on resting metabolic rate in euthyroid rats entirely caused by T3 itself?
Moreno M, Lombardi A, Beneduce L, Silvestri E, Pinna G, Goglia F, Lanni A.
Source
Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi del Sannio, 82100 Benevento, Italy.
Abstract
Because we previously reported that T3 and 3,5-diiodo-L-thyronine (3,5-T2) both increase resting metabolic rate (RMR), 3,5-T2 could be another thyroidal regulator of energy metabolism. This effect of 3,5-T2 is evident in rats made hypothyroid by propylthiouracil and iopanoic acid, not in normal euthyroid (N) rats. Possibly, under euthyroid conditions, active 3,5-T2 may need to be formed intracellularly from a precursor such as T3. We tested this hypothesis by giving a single injection of T3 to N rats and comparing the time course of the variations in RMR with those of the changes in the serum and hepatic levels of 3,5-T2. Acute injection had an evident effect on RMR, 25 h earlier, in N rats than in rats made hypothyroid by propylthiouracil and iopanoic acid, maximal values (+40%) being reached in the former at 24-26 h. In N rats, the simultaneous injection of actinomycin D with the T3 inhibited the late part of the effect (after 24 h) more strongly than the early part (14-24 h). In serum and liver, 3,5-T2 levels were increased significantly at 12-24 h after T3 injection into N rats, a time at which RMR was rising rapidly to peak. These results seem to indicate that when T3 is injected into N animals, not all the effects on RMR are attributable to T3 itself, the early effect presumably being largely because of its in vivo deiodination to 3,5-T2. Because the effects of T3 and 3,5-T2 are additive, in N rats, the two iodothyronines probably cooperate in vivo to determine the total metabolic rate.
PMID: 11796504
FFT
From the FT, possible MOA of T2 contrasted with T3
Turning now to 3,5-T2, we can say that, in contrast to T3, its effects on RMR seem to be attributable to nuclear-independent mechanisms. Some data support this conclusion. The affinity of 3,5-T2 for nuclear TRs is very low. It has been shown that TRβ1 has low affinity for 3,5-T2, with relative affinity constants 0.15% of that for T3. More recently, Ball et al. have shown that TRβ2 binds 3,5-T2 more avidly than do the other TRs, this apparent affinity remains substantially (40-fold) less than that for T3. The same authors reported that 3,5-T2 is approximately 1000-fold less potent than T3 in dissociating TRβ1 homodimers from a TRE, thus indicating that the relative ability of 3,5-T2 to bind to and produce conformational changes in a TR is consistent with its relatively low binding affinity. Moreover, an extranuclear mechanism of action of 3,5-T2 fits well with our data showing that 3,5-T2 binds to mitochondrial components and with our more recent data showing that 3,5-T2 has a very rapid effect on glucose-6-phosphate-dehydrogenase activity that is independent of protein synthesis. In addition, 3,5-T2 is able to stimulate the activity of the cytochrome c oxidase complex, and the subunit Va of this complex has been identified as a binding site for 3,5-T2. Recently, Kadenbach and co-workers have suggested that 3,5-T2 is able to decrease the efficiency of the cytochrome oxidase complex by inducing a reduction in proton-pumping.
Some more general information about the thyromimetic properties of T2
J Mol Endocrinol. 1997 Oct;19(2):137-47.
3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro.
Ball SG, Sokolov J, Chin WW.
Source
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
Recent data have suggested that the iodothyronine, 3,5-diiodo-l-thyronine (T2), has selective thyromimetic activity. In vivo, T2 has been shown to suppress TSH levels at doses that do not produce significant peripheral manifestations of thyroid hormone activity. Furthermore, T2 has been shown to produce smaller increments in peripheral indices of thyroid status than does T3, when doses resulting in equivalent suppression of circulating TSH are compared. We have assessed the selective thyromimetic activity of T2 in vivo and in vitro, and performed in vitro studies to assess the potential molecular basis for these selective properties. T2 was 100-fold less potent than T3 in stimulating GH mRNA levels in GH3 cells. In contrast, the iodothyronines were almost equivalent in their ability to downregulate TRbeta2 mRNA levels in this cell line. Both 3,3'-diiodo-L-thyronine and thyronine exhibited no significant thyromimetic effects on either process. In vivo, doses of T2 and T3 that were equivalent in their induction of hepatic malic enzyme (ME) mRNA did not produce equivalent suppression of circulating TSH, with T2 being only 27% as effective as T3. T2 was up to 500-fold less potent than T3 in displacing [125I]-T3 from in vitro translated specific nuclear receptors (TRs) and GH3 cell nuclear extracts. Electrophoretic mobility shift assays, assessing the ability of T2 to produce dissociation of TRbeta1 homodimers from inverted palindrome T3 response elements, indicated that T2 was also 1000-fold less potent than T3 in this respect. These data confirm that T2 has significant thyromimetic activity, and that this activity is selective both in vivo and in vitro. However, there are no data to support a selective central effect, T2 being relatively more potent in stimulating hepatic ME mRNA than in suppression of TSH in vivo. The basis for this differential thyromimetic activity is not selective affinity of the different TR isoforms for T2, or divergent properties of T2 in competitive binding and functional assays in vitro.
PMID: 9343306
FFT
An interesting nugget from the FT, this would appear to support the Italian's finding that T2 was not suppressive of endogenous thyroid production at physiologic doses.
However, we show that at in vivo doses of T2 and T3 resulting in equivalent induction of ME gene expression, T2 is significantly less potent in suppressing plasma TSH.
