**5.1. Leptin**

After weight loss, leptin levels decrease [178-180], as well TSH and T3 reduces to normal levels [92, 93, 112]. In starvation conditions, serum leptin levels decrease and thyroid hormones levels are quickly supressed, leading to a consequent reduction in energy expenditure [83].

Obesity and Weight Loss: The Influence of Thyroid Hormone on Adipokines 229

when the animals were refed or after insulin infusion. T3 had no effect on resistin mRNA levels

Normalization of circulating thyroid hormones was accompanied by a significant decrease in resistin concentrations [126]. Others showed that hyperthyroid patients exhibit a significant decrease in resistin levels compared with euthyroid individuals, and the normalization of circulating thyroid hormones was not accompanied by any significant change in resistin levels [127]. After adjusting the weight by the body mass index, the resistin levels in hyperthyroid patients were similar to euthyroid subjects [128] (Figure 4).

The association between thyroid hormone and resistin in weight loss present conflicting

Negative correlation between obesity and circulanting adiponectin has been well accept,

Experimental study on caloric restriction showed increased levels of circulating adiponectin [191]. Accordingly, Zhu et al. [194] showed that calorically restricted animals exhibited a significant increase in plasma adiponectin levels accompanied by significant decline in triglyceride levels, showing that adiponectin levels are inversely proportional to the degree

Thyroid hormones perform a central role in adipose tissue metabolism regulation [83], which produces the biologically active substances adipocytokines, or adipokines, that include adiponectin [127, 194], indeed thyroid hormones share some physiological actions with adiponectin, such as reduction of body fat by increased thermogenesis and lipid

The interaction between thyroid hormones and adiponectin concentration remains unclear. In humans, hyperthyroidism has been associated with both similar [128, 195] and elevated adiponectin concentrations [196], while experimental study with hyperthyroid rats found an increase in adiponectin serum concentration [133]. In agreement, some data shown that therapy to normalize hyperthyroidism significantly reduced circulating adiponectin levels [197]. In contrast Luvizotto et al. [189] show that thyroid hormone, at the doses of 5 and 25 μg T3 / 100 g BW, diminishes adiponectin gene expression, suggesting that thyroid hormone modulates negatively adiponectin expression in calorie-restricted obese rats (Figure 4).

*TNF-α* - The first information about the TNF-α biological effects indicated an involvement in insulin resistance, weight loss and anorexia. The increase in lipolysis result from TNF-α stimulus in hormone-sensitive lipase expression, leading to decreased activity of lipoprotein lipase. However, more recent investigations have revealed a molecular mechanism of weight loss on TNF-α levels, showing TNF-α expression is increased in obesity and

and adiponectin concentration increases concomitantly to weight loss [190].

in adipose tissue of obese animals submitted to calorie restriction [189].

data, requiring further studies to evaluate this relation.

**5.3. Adiponectin** 

of adiposity [192, 193].

**5.4. Others adipokines** 

oxidation [194].

Varady et al. [181] studying severely obese women have suggested that a minimum weigh loss of 5% is required to improve adipokines profile, including the reduction of leptin levels. Not only a minimal weight loss is required but a maximal weigh loss beyond which further improvements in circulating adipokine levels are no longer observed has been suggested [179, 182]. The method or diet content by which weigh loss is achieved seems to be less important than the overall weight loss [179, 183].

As mentioned before, studies investigating the correlation between thyroid hormones and leptin levels present conflicting results. Luvizotto et al. showed that administration of physiologic levels of T3 increases leptin mRNA expression with no influence on body weight in calorie-restricted obese rats [108], while administration of supraphysiological T3 dose promotes weight loss and diminishes serum levels and gene expression of leptin [108] (Figure 3). Again, as Syed et al. [106] reported, the effects of thyroid hormones in leptin concentrations might be indirect trough the regulation of fat mass (Figure 4). The decline of TSH release and T3 concentrations associated with decrease in leptin levels after weight loss may contribute to the compensatory reductions of energy expenditure and catabolism that typically accompany weight loss [184].

As both thyroid hormones and leptin have major roles in energy balance and regulation of body weight, an interaction between these hormones could not be discarded to achieve or maintain weight loss but further studies are necessary to elucidate the relationship between leptin and thyroid hormones.
