Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration

Abstract

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

Thermogenesis and longevity in mammals. Thyroxin model of accelerated aging

“…Thermoregulatory center, which is located in the hypothalamus, is regulated by hormones of the thyroid and adrenal glands (Little et al, 2013;Walrand et al, 2014). We found that the IH increases the content of mitochondria in the liver, induces an increase in liver relative weight changes, induces changes in the structure of mitochondrial membranes, and uncouples oxidative phosphorylation, which strongly suggest that the main target for thyroxin in the IH model is the mitochondria.…”

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

“…The current study suggests that T 4 , an inexpensive, toxicologically very well-defined hormone that has been systemically administered in clinical medicine for decades (Biondi and Wartofsky, 2014;Topliss and Soh, 2013) and is intracutaneously deiodinated to T 3 (van Beek et al, 2008), could serve in the treatment of skin conditions and pathologies connected with a decline in mitochondrial function (Boulton et al, 2015), intrinsic and extrinsic skin aging (Anderson et al, 2014; M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 7 Berneburg, 2008;Gilchrest, 2013;Glass et al, 2013;Grillon et al, 2012;Kaneko et al, 2012;Oyewole et al, 2014). Topical application of T 4 is expected to reduce the well-known adverse effects associated with elevated systemic TH levels (Kharlip and Cooper, 2009;Taylor et al, 2013;Walrand et al, 2014). Interestingly, topical T 3 has already been shown to promote murine skin wound healing and hair growth in vivo (Safer, 2012;Safer et al, 2005), while a topically applied TH analogue counteracted glucocorticoid-induced human skin atrophy (Yazdanparast et al, 2006).…”

Bee Pollen Improves Muscle Protein and Energy Metabolism in Malnourished Old Rats through Interfering with the Mtor Signaling Pathway and Mitochondrial Activity

“…Besides an effect on the muscle protein synthesis rate, refeeding with fresh bee pollen led to increased muscle mitochondrial function in the old malnourished rats. We focused on mitochondria due to its increasingly important role in explaining aging-related loss of muscle mass and strength, in particular during malnutrition [ 25 , 55 ]. We observed that the 5% and 10% fresh pollen refeeding diet triggered an increase in CS activity in the plantaris muscle of food-restricted old rats.…”

“…, isoform expression, allosteric control and phosphorylation, it likely represents the rate-limiting step in energy production [ 57 ]. Previous studies [ 25 , 58 , 59 ] have highlighted that muscle mitochondrial capacity is dependent not only on mitochondrial density, but also on the existence of qualitative differences in mitochondrial functioning. Building on our previous work [ 45 ], we propose that the fresh bee pollen-supplemented diet-induced improvement in functional mitochondria may be the result of attenuated mitochondrial oxidant emission, increased oxidant scavenging and decreased cellular oxidative damage, all of which could be expected to contribute to maintaining the functional integrity of the mitochondrial machinery.…”

“…The homogenate was centrifuged at low speed (600× g ), and the supernatant was collected, put through 5 freeze-thaw cycles and mixed thoroughly before measuring enzyme activities. Activities of citrate synthase (CS), a key enzyme of the Krebs cycle, 3-hydroxy acyl CoA dehydrogenase, a key enzyme of β-oxidation, and of complexes II to IV of the respiratory chain were spectrophotometrically assayed in the supernatant fraction, as previously described [ 25 , 26 ]. All measures were performed in triplicate.…”