Elsevier

Vitamins & Hormones

Volume 90, 2012, Pages 57-94
Vitamins & Hormones

Chapter Three - Nutritional and Hormonal Modulation of Adiponectin and its Receptors adipoR1 and adipoR2

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Abstract

Adiponectin is the most abundant plasma protein synthesized mostly by adipose tissue and is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. Adiponectin effects are mediated via two receptors, adipoR1 and adipoR2. Several hormones and diet components that are involved in insulin resistance may impair insulin sensitivity at least in part by decreasing adiponectin and adiponectin receptors. Adiponectin expression and serum levels are associated with the amount and type of fatty acids and carbohydrate consumed. Other food items, such as vitamins, alcohol, sodium, green tea, and coffee, have been reported to modify adiponectin levels. Several hormones, including testosterone, estrogen, prolactin, glucocorticoids, catecholamines, and growth hormone, have been shown to inhibit adiponectin production, but the studies are still controversial. Even so, adiponectin is a potential therapeutic target in the treatment of diabetes mellitus and other diseases associated with hypoadiponectinemia.

Introduction

Adiponectin is an abundant plasma protein with concentrations higher than those of other hormones corresponding to 0.01–0.05% of the total serum proteins (Arita et al., 1999, Nakano et al., 1996). It is primarily synthesized by adipocytes but has also been detected in skeletal muscle (Delaigle, Jonas, Bauche, Cornu, & Brichard, 2004), cardiomyocytes (Pineiro et al., 2005), osteoblasts (Berner et al., 2004), lymphocytes (Crawford, Peake, Price, Morris, & Irvine, 2010), adrenal gland (Paschke et al., 2010), placenta (Caminos et al., 2005), testis (Caminos et al., 2008), ovary (Chabrolle, Tosca, & Dupont, 2007), pituitary gland (Rodriguez-Pacheco et al., 2007), and liver tissue (Ma et al., 2009). Secreted adiponectin has different multimeric forms. Globular adiponectin exists as a trimer and full-length adiponectin exists in three forms: a low-molecular weight trimer (LMW), a medium-molecular weight (MMW) hexamer, and a high-molecular weight oligomer (HMW) (Hada et al., 2007). HMW is considered the most metabolically active form and a reduction in this form is related to insulin resistance, diabetes, and obesity (Lara-Castro et al., 2006, Wang et al., 2008).

Unlike other adipokines produced by adipose tissue, plasma levels of adiponectin are inversely correlated with body mass index, visceral adiposity, plasma levels of triglycerides, and low-density lipoprotein (Arita et al., 1999, Lihn et al., 2004, Maeda et al., 1996, Yamamoto et al., 2002).

The inverse correlation between plasma levels of adiponectin and obesity is probably a result of altered gene expression induced by oxidative stress and hypoxia (Soares et al., 2005, Trayhurn et al., 2008). Adiponectin is an insulin-sensitive hormone and plays a central role in lipid and glucose metabolism (Lihn, Pedersen, & Richelsen, 2005). It augments lipid oxidation in skeletal muscle and myocytes (Fruebis et al., 2001, Yamauchi et al., 2001) and reduces hepatic glucose production in liver and hepatocytes (Berg et al., 2001, Combs et al., 2001). In addition, adiponectin possesses antiatherogenic activities and anti-inflammatory effects (Lihn et al., 2005, Ouchi et al., 2001).

All these metabolic processes are mediated via two adiponectin receptors, adipoR1 and adipoR2, that activate its downstream signaling pathways mainly by activating adenosine monophosphate-activated kinase (AMPK) and peroxisome proliferator-activated receptors alpha (PPAR-α). In mouse, it was observed that adipoR1 receptor acts via AMPK pathway, whereas adipoR2 through PPAR-α signaling (Yamauchi et al., 2007). AdipoR1 has a strong affinity for globular adiponectin and full-length adiponectin and is mainly expressed in the liver (Yamauchi et al., 2003). AdipoR2 exhibits an intermediate affinity for globular and full-length adiponectin and is mainly expressed in muscle (Beylot, Pinteur, & Peroni, 2006). Adiponectin receptors have also been detected in pancreatic beta cells (Kharroubi, Rasschaert, Eizirik, & Cnop, 2003), macrophages (Chinetti, Zawadski, Fruchart, & Staels, 2004), osteoblasts (Berner et al., 2004), adrenal gland (Paschke et al., 2010), human endometrium (Takemura et al., 2006), testis (Caminos et al., 2008), ovary (Chabrolle et al., 2007), hypothalamus (Qi et al., 2004), endothelial cells (Motoshima, Wu, Mahadev, & Goldstein, 2004), placenta (Caminos et al., 2005), and in adipose tissue (Rasmussen et al., 2006), with adipoR1 being expressed 10–15-fold higher than adipoR2 (Beylot et al., 2006). T-cadherin, a tumor-suppressor protein, was identified as the third adiponectin receptor by its ability to specifically bind the HMW isoforms of adiponectin. This receptor is abundantly expressed in the cardiovascular system and also in muscle cells (Hug et al., 2004).

Several hormones and diet components that are involved in insulin resistance may impair insulin sensitivity at least in part by decreasing adiponectin and adiponectin receptors expression and/or secretion. In this chapter, we review current studies on the effect of some of these factors on adiponectin system.

Section snippets

Fatty acids

A high level of dietary fat in the diet is a major factor in promoting weight gain, obesity, and insulin resistance. Different studies have shown that the excess of fat on diet decreases adiponectin gene transcription (Berk et al., 2005, Barnea et al., 2006, Bullen et al., 2007, Boullu-Ciocca et al., 2008; Mullen et al., 2010, Zhang et al., 2007). This reduction may play a causal role in the development of insulin resistance. Further, decreasing the expression of adipoR1 and adipoR2 leads to a

Adrenal hormones

The adrenal steroid hormones, glucocorticoids, are involved in glucose and lipid metabolism, and insulin secretion, and contribute to the development of obesity and insulin resistance (Andrews and Walker, 1999, Müssig et al., 2010).

Studies in vitro and in vivo showed inhibition of adiponectin expression and reduction on plasma adiponectin levels by glucocorticoids (Degawa-Yamauchi et al., 2005, Fallo et al., 2004, Fasshauer et al., 2002, Halleux et al., 2001, Jang et al., 2008). Viengchareun,

Conclusion

In this chapter, we reviewed the effects of some diet components and hormonal factors involved in the regulation of adiponectin and adiponectin receptors in both experimental and human models. The conflicting results about the effects of food items on adiponectin levels are possibly due to differences in the amount and frequency of the food item consumed, the dietary context or nutritional status and the explanation for the discrepancies regarding the effects of hormones on adiponectin levels

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