**1. Introduction**

The primary function of adipose tissue is storing energy in triacylglycerol (TG) form, neutralizing the excess of circulating lipids and saving non-adipose tissues of a fat overload. Under normal conditions, in the postprandial state, there is lipogenic endocrine system stimulation, allowing that positive energy balance can be stored as TG in adipose tissue, a process called lipogenesis. In contrast, the mobilization of fat in adipocytes occurs through the hydrolysis of TG by hormone sensitive lipase (HSL), a phenomenon called lipolysis. At the center of this interface - lipolysis and lipogenesis - is the insulin hormone, which exerts a potent inhibitory role on the HSL, allowing lower rates of lipolysis and hence, highest fat mass [1]. However, adipose tissue is not only a passive stock organ of triacylglycerol, being currently recognized as an endocrine organ with multiple functions [1, 2]. Produces several biologically active substances called adipokines, among them tumor necrosis factor- (TNF-), monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), leptin, resistin and adiponectin. These substances actively participate in, among others, body energy regulation, mainly, by endocrine, paracrine and autocrine signals, which allow the adipocyte play a metabolic role in other tissues [3-5].

However, in obesity there is an imbalance in adipokines production, a fact which, together with the inability to store fat in the adipocytes, results in a process of adipose tissue dysfunction [6], a known risk factor for developing obesity-associated metabolic disorders [1, 2, 6]. This fact occurs because the adipocytes (hypertrophic and hyperactive) initiates the production of adipokines and chemotactic factors (such as MCP-1), which attract macrophages into the adipose tissue [7]. Consequently there is a synergistic interaction on

© 2012 Luvizotto et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

proinflammatory adipokines production - mainly TNF-α - and antagonistic on adiponectin. These substances lead to insulin resistance, reducing the lipogenic action of insulin in adipocytes, which results in higher rates of lipolysis in the adipose tissue [8, 9]. On the other hand, calorie restriction affects the regulation of adipose tissue gene expression, normalizing the adipokines changes observed in obesity [10].

Obesity and Weight Loss: The Influence of Thyroid Hormone on Adipokines 215

With its gene identified in 1994 [16] leptin is the adipokine most studied and thenceforth it has been identified more than 30 biochemical products secreted by adipocytes. Leptin is a peptidic hormone with 167 amino acids and 16kDa of molecular weight and synthesized from the "ob" gene in adipocytes, being more common in subcutaneous adipose tissue than in visceral fat [17]. Besides to be considered an important lipostate, or energy balance regulator according to body fat mass in long-term [18, 19] has been implicated in the regulation of immune, respiratory and reproductive systems [20]. The term Leptin comes from Greek "leptos" which means "thin" due to the fact that this protein lead to increased energy expenditure and act on satiety signals in hypothalamus, reducing caloric intake [21]. The expression and circulating leptin levels are controlled by a number of factors that may increase its secretion (insulin, glucocorticoids, TNF-α, estrogens, thyroid hormone and CCAAT/enhancer-binding protein-alpha) or decrease (Beta3-adrenergic activity, androgens , free fatty acids, GH, and peroxisome proliferator-activated receptor-gamma agonists) depending on the physiological assembly expressed by the body, especially on satiety and

When circulating this adipokine reaches various body tissues as pancreas, increasing insulin secretion; liver, causing a satiety sensation by the increase in glucose production and increasing energy expenditure; hypothalamus, increasing stimulation of hypothalamicpituitary-adrenal axis, and decreasing the stimulus of hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis; muscle tissue, increasing glucose uptake and

Many of the effects of leptin result from their actions on the central nervous system, particularly in the hypothalamus, which acts in satiety and appetite regulation. Reaching these tissues after crossing the blood-brain barrier, leptin acts in the arcuate nucleus where there is a large concentration of leptin receptors, when binding to reduce the action of neurons that use neuropeptide Y (NPY) signaling and agouti-related protein (ARGP). NPY is a peptide of 36 amino acids, synthesized mainly in the arcuate nucleus, which projects to the paraventricular nucleus, ventromedial, perifornical and lateral, also involved in energy balance regulation. It is the most potent orexigenic. The ARGP also synthesized in the arcuate nucleus, also is projected to paratentricular nucleus, ventromedial and lateral, acting as a melanocortin system analogue on receptors MC-3 and MC-4, stimulating food intake. Leptin acts by decreasing the activity of these orexigenics signals, inhibiting food intake and increasing energy expenditure by activating the sympathetic nervous system [24, 25]. Also in the hypothalamus, leptin activates neurons pro-opiomelanocortin (POMC) producing alpha-melanocyte stimulating hormone (alpha-MHS). All substances expressed in this system are anorexigenics, ie, act on reducing food intake [14]. This product acts on malanocortin-4 receptors and also on neurons that express cocaine and amphetamineregulated transcript (CART). POMC/CART neurones also have projections to the lateral hypothalamus and paraventricular nucleus, with a reciprocal innervation of these nuclei to the arcuate nucleus. Both alpha-MSH and CART are potent anorexigenic agents. The

**2.1. Leptin** 

energy intake [22].

metabolism [23].

**Figure 1.** Adapted from van Kruijsdijk et al, 2009 [6]. In obesity the hypertrophic and hyperactive adipocytes initiate the production of MCP-1, which attract macrophages into the adipose tissue, increasing proinflammatory adipokines production (mainly TNF-α) and decreasing adiponectin production, leading to insulin resistance and inflammation. The weight loss process revert this alterations, improving insulin resistance and inflammation. FFA: fatty free acids; PAI1: Plasminogen activator inhibitor 1; TNFα: tumor necrosis factor-α; MCP1: monocyte chemoattractant protein 1; IL6: interleukin 6.

In this chapter will be revised about the influence of thyroid hormones on adipokines in obesity and weight loss. Also will be discussed the physiological role of adipokines as well as the effect of obesity and weight loss on the adipokines.
