*Urszula Puchta1, Elwira Siewiec1, Lukasz Szczerbinski1, Anna Citko2, Hady Razak Hady3, Adam Jacek Kretowski1, 2
The role of gastrointestinal hormones in the pathogenesis and the treatment of obesity
Rola hormonów przewodu pokarmowego w patogenezie i leczeniu otyłości
1Department of Endocrinology, Diabetology and Internal Medicine, Faculty of Medicine, Medical University of Bialystok, Poland
2Clinical Research Center, Faculty of Medicine, Medical University of Bialystok, Poland
3Ist Department of General and Endocrinological Surgery, Faculty of Medicine, Medical University of Bialystok, Poland
Streszczenie
Otyłość jest coraz większym problemem na świecie i dotyka codziennie coraz większej części społeczeństwa. Jej głównymi przyczynami są zaburzenia ośrodków głodu i sytości oraz zaburzenia metaboliczne związane z nieprawidłową gospodarką kwasów tłuszczowych, kwasów żółciowych, węglowodanów i lipidów. Niemniej jednak, dokładne mechanizmy rozwoju tej choroby są nadal słabo poznane. W ostatnich latach coraz więcej uwagi skupia się na roli, jaką pełnią hormony żołądkowo-jelitowe w patogenezie otyłości, która również zapewnia nowe punkty uchwytu w zakresie terapii farmakologicznej.
Celem niniejszej pracy jest przedstawienie roli hormonów żołądkowo-jelitowych w patogenezie i leczeniu otyłości. Zaburzenia, które wynikają z otyłości, zależą głównie od nieprawidłowej koncentracji hormonów żołądkowo-jelitowych, którymi są: adiponektyna, leptyna, peptyd YY (PYY) i FGF-19.
Kontrola i regulacja stężenia krążących hormonów żołądkowo-jelitowych jest ważna dla utrzymania prawidłowej masy ciała i homeostazy energetycznej. Obecnie najskuteczniejszymi metodami kontroli stężenia tych hormonów są terapia farmakologiczna i zabieg bariatryczny, które mają korzystny wpływ również na choroby współwystępujące związane z otyłością.
Summary
Obesity is an increasing problem in the world and affects a growing part of society on everyday basis. Its main causes are disorder of the hunger and satiety centers and metabolic disorders regarding to improper management of fatty acids, bile acids, carbohydrates and lipids. However, the exact mechanisms of the disease development are still poorly understood. In recent years more attention is focused on the role of gastrointestinal hormones in the pathogenesis of obesity, which also delivers new targets for pharmacotherapy.
This review aims to present the role of gastrointestinal hormones in the pathogenesis and the treatment of obesity. The abnormalities present in obese patients refer mainly to disturbances in concentration of adiponectin, leptin, peptide YY (PYY) and FGF-19.
Controlling and regulating the concentration of circulating gastrointestinal hormones is important in maintaining proper body mass and energy homeostasis. Currently, the most effective methods controlling the concentration of these hormones are pharmacology and bariatric surgery which improve also obesity-related comorbidities.
Introduction
Obesity is one of the most common metabolic disorders nowadays and it is a growing problem among world’s population. According to World Health Organization (WHO), obesity has tripled worldwide since 1975 (1). It is believed that one out of five people will be obese until 2025 (2). As a matter of fact in 2016 upward of 1.9 billion adults over 18 years old were overweight, including 650 million classified as obese (1).
Obesity, defined as an excessive accumulation of body fat, exceeding its physiological needs and adaptive abilities, which can lead to adverse health effects (1, 3). It is categorized on the basis of the body mass index (BMI). BMI above 25 kg/m2 indicates overweight, while BMI exceeding 30 kg/m2 distinguishes obesity (4).
Sedentary lifestyle and “western” diet are main factors contributing to the global obesity pandemic. This problem inevitably poses a challenge to global economy and public healthcare (2, 3).
It has been found that both obesity and overweight are associated with increased risk of comorbidities including type 2 diabetes mellitus, cardiovascular disease, metabolic syndrome and many others, which may lead to disability or shorten the life expectancy (3).
In reference to obesity the gastrointestinal system is a significant source of nourishment (3). Gastrointestinal hormones play an important role in regulation and control of food intake (5). Along with the growing problem of obesity in the world, gastrointestinal hormones have become one of the most popular topics of scientific research (3). These hormones exert exocrine actions, affect gut motility and also influence the secretion of insulin. They modulate releasing peptide neurotransmitters in the brainstem and abovementioned hypothalamic centres via gut-brain axis (5).
Consequently, this review focuses on the role of gastrointestinal hormones in the pathogenesis and the treatment of obesity. We took an in-depth look at the following hormones: adiponectin, leptin, peptide YY (PYY) and FGF-19.
Review
Adiponectin
Adiponectin, known as adipocyte complement-related protein, is composed of 244 amino acids with a weight of approximately 30 kDa (6). Adiponectin is a cytokine produced by mature fat cells (6, 7). The hormone principally modulates fatty acid catabolism and glucose homeostasis (7). This adipokine is involved in inhibiting energy expenditure and increasing lipid accumulation in fat cells, which contributes to the increase in adipocyte differentiation and inhibition of lipolysis (8).
The level of adiponectin in serum of obese people is decreased. Adiponectin levels correlate inversely with adipose tissue and WHR, which shows a significant enhancement after weight loss (7). It is also known that plasma adiponectin concentration is negatively correlated with plasma insulin concentrations. What is more, the latest research proves that the level of adiponectin increases following bariatric surgery. Weight reduction in obese patients undergoing bariatric surgery is associated with increased insulin sensitivity and reduced insulin secretion (9). Due to the fact that the secretion of adiponectin is impaired as a result of obesity, the bariatric surgery is a practical therapeutic approach to restore the tissue’s ability to produce adiponectin.
Leptin
Leptin is a protein composed of 146 amino acids with a molecular weight of 16 kDa (10). It is secreted mostly by adipocytes (7). Leptin transport is regulated by two receptors: ObRa, which is involved in the transport of leptin across the blood-brain barrier, and ObRe, which acts inversely to ObRa (11). These receptors are found throughout the body particularly in the central nervous system (12).
Leptin is a hormone that participates in regulating the energy management of the body via controlling glucose metabolism and appetite (7). It passes across the blood-brain barrier to act trough its receptor, inhibiting oxygenicity and stimulating anorexigenic neuropeptides located in the arcuate nucleus of the hypothalamus, which leads to reduction in food intake (13).
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Piśmiennictwo
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*Urszula Puchta
Klinika Endokrynologii, Diabetologii i Chorób Wewnętrznych
Uniwersytecki Szpital Kliniczny
w Białymstoku
ul. Marii Skłodowskiej-Curie 24A,
15-276 Białystok
tel.: +48 (85) 831-81-56
puchta.urszula@gmail.com
