Chapter Three - Nutritional and Hormonal Modulation of Adiponectin and its Receptors adipoR1 and adipoR2
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
References (244)
- et al.
Carbohydrate restriction, as a first-line dietary intervention, effectively reduces biomarkers of metabolic syndrome in Emiratiadults
The Journal of Nutrition
(2009) - et al.
Effect of experimental hypo and hyperthyroidism on serum adiponectin
Metabolism
(2007) - et al.
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity
Biochemical and Biophysical Research Communications
(1999) - et al.
Adiponectin and its receptors are expressed in bone-forming cells
Bone
(2004) - et al.
Expression of the adiponectin receptors AdipoR1 and AdipoR2 in lean rats and in obese Zucker rats
Metabolism
(2006) - et al.
Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice
Diabetes & Metabolism
(2008) - et al.
Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study
The American Journal of Clinical Nutrition
(2005) - et al.
Fructose alters adiponectin, haptoglobin and angiotensinogen gene expression in 3T3-L1 adipocytes
Nutrition Research
(2010) - et al.
The 1alpha,25-dihydroxy Vitamin D3 receptor preferentially recruits the coactivator SRC-1 during up-regulation of the osteocalcin gene
The Journal of Steroid Biochemistry and Molecular Biology
(2007) - et al.
Effect of ovarian hormones on serum adiponectin and resistin concentrations
Fertility and Sterility
(2009)
Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARa, PPARg, and LXR
Biochemical and Biophysical Research Communications
Blood ghrelin, resistin, and adiponectin concentrations during the normal menstrual cycle
Fertility and Sterility
Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver
Steroids
Influence of the crosstalk between growth hormone and insulin signalling on the modulation of insulin sensitivity
Growth Hormone & IGF Research
Fructose, weight gain, and the insulin resistance syndrome
The American Journal of Clinical Nutrition
Growth hormone is a positive regulator of adiponectin receptor 2 in 3T3-L1 adipocytes
FEBS Letters
Adiponectin gene expression is inhibited by β-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes
FEBS Letters
Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes
Biochemical and Biophysical Research Communications
Growth hormone signalling and its regulation: preventing too much of a good thing
Growth Horm IGF Res
Beta adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-alpha expression in adipocytes
European Journal of Pharmacology
Salt sensitivity is associated with insulin resistance in essential hypertension
American Journal of Hypertension
Adiponectin is expressed in the brown adipose tissue and surrounding immature tissues in mouse embryos
Biochimica et Biophysica Acta
Role of AMP-activated protein kinase and adiponectin during development of hepatic steatosis in high-fat diet-induced obesity in rats
Journal of Comparative Pathology
Selective purification and characterization of adiponectin multimer species from human plasma
Biochemical and Biophysical Research Communications
Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue
Biochemical and Biophysical Research Communications
Influence of thyroid dysfunction on serum concentrations of adipocytokines
Cytokine
Brain adipocytokine action and metabolic regulation
Diabetes
Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism
Clinical Endocrinology
Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats
Endocrine
Glucocorticoids and insulin resistance: Old hormones, new targets
Clinical Science (London, England)
Hypoadiponectinemia in lean lactating women: Prolactin inhibits adiponectin secretion from human adipocytes
Endocrine Journal
Serum adiponectin and leptin in a patient with Cushing's syndrome before and after adrenalectomy
Internal Medicine
Regulation of gene expression by alpha-tocopherol
Biological Chemistry
Adiponectin translation is increased by the PPAR agonists pioglitazone and ω-3 fatty acids
American Journal of Physiology. Endocrinology and Metabolism
A high-fat diet has a tissue-specific effect on adiponectin and related enzyme expression
Obesity
Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome
Nutrition
Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects
Internal and Emergency Medicine
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Nature Medicine
Adiponectin levels during low- and high-fat eucaloric diets in lean and obese women
Obesity Research
Alcohol consumption, mediating biomarkers, and risk of type 2 diabetes among middle-aged women
Diabetes Care
Glucose tolerance and insulin secretion after adrenalectomy in mice made obese with gold thioglucose
The Journal of Endocrinology
Analysis of serum adiponectin, resistin and leptin levels in children and adolescents with autoimmune thyroid disorders
Journal of Pediatric Endocrinology & Metabolism
Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal
Thyroid
Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels
The Journal of Clinical Endocrinology and Metabolism
Postnatal programming of glucocorticoid metabolism in rats modulates high-fat diet-induced regulation of visceral adipose tissue glucocorticoid exposure and sensitivity and adiponectin and proinflammatory adipokines gene expression in adulthood
Diabetes
Adipocyte prolactin: Regulation of release and putative functions
Diabetes, Obesity & Metabolism
Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: Systematic review and meta-analysis of interventional studies
British Medical Journal
Sex hormones, insulin sensitivity, and diabetes mellitus
ILAR Journal
Effects of different fatty acids and dietary lipids on adiponectin gene expression in 3T3-L1 cells and C57BL/6J mice adipose tissue
Pflügers Archiv
Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice
American Journal of Physiology. Endocrinology and Metabolism
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Adiponectin and adiponectin receptors in common carp (Cyprinus carpio): Tissue distribution and their expressions in response to high-carbohydrate and high-lipid diets
2022, Aquaculture ReportsCitation Excerpt :Adiponectin is well known for its close association with metabolic diseases in mammals, such as obesity and insulin resistance (Berg et al., 2001; Fruebis et al., 2001), and it level is closely related to dietary carbohydrate and lipid in mammals. Plasma adiponectin levels were negatively correlated with obesity, insulin resistance, and type 2 diabetes in mammals (Khoramipour et al., 2021), and most studies showed that excess of fat or carbohydrate in the diet decreased its gene transcription and protein levels (de Oliveira et al., 2012). On the contrary, the present study showed that the high-carbohydrate diet induced adipoqa and adipoqb mRNA expression in the heart of common carp, even though it slightly reduced adipoqb transcriptional level in the white muscle, and the high-lipid diet significantly promoted adipoqa mRNA expression in the red muscle and heart.
Sex- and season-dependent differences in the expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in the hypothalamic-pituitary-adrenal axis of the Eurasian beaver (Castor fiber L.)
2020, General and Comparative EndocrinologyCitation Excerpt :The hormone is synthesized mainly by mature adipocytes in brown and white adipose tissues, and it is the most abundantly expressed adipokine (Ahima, 2006). Adiponectin is also secreted by other cells and tissues, including the central nervous system (CNS), skeletal muscles, cardiomyocytes, osteoblasts, liver, adrenals and reproductive structures (de Oliveira et al., 2012; Dobrzyn et al., 2018). The hormone plays an important role in the regulation of autonomic and neuroendocrine functions, energy homeostasis and feeding behaviour (Banerjee and Chaturvedi, 2018; Hoyda et al., 2009; Kubota et al., 2007; Rodriguez-Pacheco et al., 2007).
Effect of the emulsion of Sacha Inchi (Plukenetia huayabambana) oil on oxidative stress and inflammation in rats induced to obesity
2020, Journal of Functional FoodsCitation Excerpt :Adiponectin can activate lipoprotein lipase and, in our study, its activation would have contributed to the decrease of TG in serum. Additionally, adiponectin is able to favor the oxidation of fat through the activation of Acyl-CoA oxidase and in the present study the probable increase in lipid oxidation would have also contributed to the decrease of TG in serum and increased activity of catalase (De Oliveira, De Mattos, Silva, Mota, & Zemdegs, 2012; Ide, 2000; Kim & Choi, 2005; Rincón-Cervera et al., 2016; Xu et al., 2007). This statement would be attributed to the high ω-3 content of the emulsion of SI oil, as reported in a group of rats that were fed a high-fat diet (45% fat Kcal) for 10 weeks and then ω-3 LCPUFA.
Micronutrients in Nonalcoholic Fatty Liver Disease Pathogenesis
2018, Cellular and Molecular Gastroenterology and HepatologyCitation Excerpt :Similarly, shared pathophysiologic pathways between insulin resistance and NAFLD can provide insight into the role of micronutrients in NAFLD. For example, observational and in vivo studies have linked adiponectin deficiency with obesity, insulin resistance, and NAFLD46; and adiponectin modulation is impacted by micronutrient availability.47,48 Despite data suggesting mineral deficiencies in NAFLD patients, most data do not support insufficient mineral consumption as a possible mechanism for these deficiencies, except in the case of zinc deficiency.49–51
Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer cells
2017, Pulmonary Pharmacology and TherapeuticsCoffee and metabolic impairment: An updated review of epidemiological studies
2016, NFS JournalCitation Excerpt :These studies remarked the inverse association between coffee consumption and obesity or visceral fat area. Experimental studies reported that coffee may play a role in the expression of adipo-R2 gene, which activate its downstream signaling pathways mainly by activating AMPK and peroxisome proliferator-activated receptors alpha (PPAR-a) [89]. Coffee polyphenols and melanoidins protected the liver from damage caused by a hypercaloric diet in an animal model, and this protection was partially mediated by a reduction in liver inflammation, through increases of adipo-R2 gene and anti-inflammatory cytokines IL-4 and IL-10 [90].