Thyroid Hormone Modulates Food Intake and Glycemia via Ghrelin Secretion in Zucker Fatty rats

Abstract

Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones.

MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

“…We demonstrated that the administration of 3 mg/kg of MK-0677 resulted in an 11.6% increase in food intake and 64% weight gain in the C57BL/6 mice compared with the vehicle group. These findings were consistent with those of previous studies which reported that MK-0677 increased food intake and body weight [ 52 , 75 , 76 ]. Interestingly, MK-0677 did not increase the cumulative food intake or changes in body weight in the 5XFAD mice.…”

“…The ghrelin agonist MK-0677 has acute orexigenic effects in rodents [ 52 ]. To establish the optimal doses of MK-0677 that induce biological responses, we injected eight-week-old C57BL/6 mice with 0.1, 1, and 3 mg/kg of MK-0677 cumulatively for 10 days, as described previously [ 52 ]. The intraperitoneal administration of 1 and 3 mg/kg of MK-0677 increased food intake compared to that in the vehicle-administered group ( n = 5; Figure 1 A).…”

Potential Applications of Thyroid Hormone Derivatives in Obesity and Type 2 Diabetes: Focus on 3,5-Diiodothyronine (3,5-T2) in Psammomys obesus (Fat Sand Rat) Model

“…This result is paradoxical. However, elevated food intake might be a consequence of increase energy expenditure (our study), associated with reduced serum leptin concentrations related to hypothalamic effects after 3,5-T2 treatment [ 52 ]; or which might involve altered ghrelin secretion [ 53 ]. Indeed, previous studies have shown to depend on hypothalamic activation of the mammalian target of rapamycin pathway ( mTOR signaling) leading to amplified orexigenic agouti-related peptide, neuropeptide Y, and decreased mRNA levels of anorexigenic proopiomelanocortin in the arcuate nucleus of the hypothalamus [ 54 ] representing a strong orexigenic drive.…”

A Status Report on Autonomic Nervous System: the Indian Research Scenario during the Last Five Years

“…In an experimental study, Zucker fatty rats demonstrated acute orexigenic and hyperglycemic effects of T3 which is associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones (Patel et al, 2014). In a study with psoriatic arthritis patients, Syngle et al (2013) have concluded that cardiovascular autonomic and peripheral sympathetic neuropathy occurs in psoriatic arthritis.…”