Endocrine and Metabolic Side Effects
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
White adipose tissue acts as an endocrine organ producing a variety of hormones (adipocytokines), including adiponectin, leptin, tumor-necrosis factor alpha, and angiotensin II, which influence lipid metabolism, systemic insulin sensitivity, and inflammation. Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin performs many metabolic functions that link to energy metabolism (151,152). The hormone leptin is also a hormone predominantly secreted by adipose cells that helps to regulate energy balance by inhibiting hunger acting on receptors in the arcuate nucleus of the hypothalamus. In obesity, a decreased sensitivity to leptin occurs resulting in an inability to detect satiety despite high energy stores and high levels of leptin. The primary function of the hormone leptin is the regulation of adipose tissue mass through central hypothalamus−mediated effects on hunger, food energy use, physical exercise, and energy balance (153,154).
Pathophysiology of Diabetes
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
In type 2 diabetes, obesity and weight gain influence insulin resistance. Though genetic determinants are present, diet, exercise, and lifestyle are extensively involved. Adipose tissues increase the plasma levels of free fatty acids, which can impair insulin-stimulated glucose transport and the activity of muscle glycogen synthase. The adipose tissues are believed to have endocrine functions. They release adipocytokines that may be metabolically favorable or unfavorable. Adiponectin is an example of a metabolically favorable adipocytokine. Unfavorable adipocytokines include IL-6, leptin, resistin, and tumor necrosis factor-alpha. Insulin resistance occurring later in life is also related to intrauterine growth restriction and low birth weight. This may be in conjunction with prenatal environmental influences upon metabolism of glucose.
Impact of Lifestyle Medicine on Dysglycemia-Based Chronic Disease
James M. Rippe in Lifestyle Medicine, 2019
Lipid metabolism is also highly affected in DBCD. Increased circulating free fatty acids that result from insulin resistance contribute to pancreatic β-cell dysfunction, reduced hepatic sensitivity to insulin, macrophage activation, and low-grade systemic inflammation. Additionally, adipose tissue, which becomes highly resistant to insulin, is redistributed with increased visceral and relatively decreased subcutaneous adipose tissue. These abnormalities in adiposity and adipocyte function affect adipokine production and can generate a state of low adiponectin, high resistin, and high chemerin that further drives insulin resistance.29 The triad of abnormal adipose tissue mass, distribution, and function contributing to metabolic risk is termed adiposity based chronic disease and represents an expanded view and working model of obesity, while also highlighting interactions with dysglycemia based chronic disease.30
Promising predictors of checkpoint inhibitor response in NSCLC
Published in Expert Review of Anticancer Therapy, 2020
Friedlaender Alex, Addeo Alfredo
While body mass index (BMI) is linked to cardiovascular morbidity and mortality, the link with oncologic outcomes is more debated. An elevated BMI is known to be associated with chronic low-grade inflammation [43]. It is believed that this could be linked to dysregulated cytokine production, through altered adipokine function. The result may be dysfunctional immune cell activity caused by increased BMI. A recent, large-scale retrospective analysis of patients with advanced NSCLC treated with ICPIs found that a BMI ≥ 25, representing the category of overweight patients, had improved clinical outcomes, including response rates and OS compared to those with a BMI < 25 [44–46]. Given the immune-dysfunction caused by adiposity, ICPIs may revert the BMI-linked immuno-suppression, thus conferring superior tumor control. This is the subject of much research and is not ready for considering in clinical practice at this time.
Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome
Published in Gynecological Endocrinology, 2019
Murat Alan, Beril Gurlek, Alpay Yilmaz, Murat Aksit, Behnaz Aslanipour, Ibrahim Gulhan, Calan Mehmet, Cuneyt Eftal Taner
Adipose tissue is a metabolically active organ. It secretes a variety of cytokines ‘adipokine’ which have a crucial role in the regulation of some metabolisms including glucose and lipid metabolisms as well as insulin resistance. Adipose tissue dysfunction is related to metabolic disturbances in women with PCOS regardless being obese. Cytokine levels are altered in women with PCOS. Alteration of adipokines such as adiponectin can affect insulin secretion and insulin action [14–16]. A useful feature of asprosin which is a newly identified adipokine is its association with insulin resistance [1]. Despite this interest, no one to the best of our knowledge has studied the effect of asprosin associated with insulin resistance PCOS women. For this reason, in the present study, we explored the levels of asprosin in women with PCOS as compared with controls. We found that asprosin levels were higher in women with PCOS than control. Asprosin levels showed an independent association with insulin resistance and FAI. We also highlight that the subjects with the highest tertile of asprosin had the highest likelihood of having PCOS risk with respect to the subjects with the lowest tertile of asprosin.
Increased visceral adiposity index associated with sexual dysfunction in men
Published in The Aging Male, 2018
Murat Dursun, Huseyin Besiroglu, Suleyman Sami Cakir, Alper Otunctemur, Emin Ozbek
Obesity induces alterations in cytokine and adipokine secretions. These proinflammatory factors contribute to endothelial dysfunction and insulin resistance, pathologies that increase the risk of ED [18]. Obesity is a proinflammatory state resulting in increased release and secretion of proinflammatory cytokines and adipokines, free fatty acids and estrogens from adipose tissue. These increases are important risk factors that may contribute to the development of metabolic syndrome and type 2 diabetes as well as androgen deficiency [19,20]. Also, obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had the patients [21,22]. Inversely, studies show that long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters such as body weight, waist circumference and body mass index and improves metabolic syndrome and health-related quality of life [23,24]. On the other hand, as previously reported [25], testosterone replacement therapy was associated with improvements in quality of life, ED and lower urinary tract symptoms.