Targeting of the central histaminergic system for treatment of obesity and associated metabolic disorders

2006 ◽  
Vol 67 (8) ◽  
pp. 651-665 ◽  
Author(s):  
Kjell Malmlöf ◽  
Rolf Hohlweg ◽  
Karin Rimvall
2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.


2020 ◽  
Vol 295 (44) ◽  
pp. 14878-14892
Author(s):  
Dong Young Kim ◽  
Mi Jin Choi ◽  
Tae Kyung Ko ◽  
Na Hyun Lee ◽  
Ok-Hee Kim ◽  
...  

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT1 receptor) signaling. Here, we report that losartan, a selective AT1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT1 receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The in vivo browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, in vivo apelin knockdown by adeno-associated virus carrying–apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT1 receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.


2020 ◽  
Vol 192 ◽  
pp. 112172
Author(s):  
Yong Rao ◽  
Zhao Xu ◽  
Yu-Tao Hu ◽  
Chan Li ◽  
Yao-Hao Xu ◽  
...  

2021 ◽  
pp. 161-168
Author(s):  
AV Sirotkin ◽  
A Kolesarova

This paper reviews provenance, chemical composition and properties of tea (Camelia sinensis L.) and coffee (Coffee arabica, L. and Coffea caniphora, L.), their general health effects, as well as the currently available knowledge concerning their action on fat storage, physiological mechanisms of their effects, as well as their safety and recommended dosage for treatment of obesity. Both tea and coffee possess the ability to promote health and to prevent, to mitigate and to treat numerous disorders. This ability can be partially due to presence of caffeine in both plants. Further physiological and medicinal effects could be explained by other molecules (theaflavins, catechins, their metabolites and polyphenols in tea and polyphenol chlorogenic acid in coffee). These plants and plant molecules can be efficient for prevention and treatment of numerous metabolic disorders including metabolic syndrome, cardiovascular diseases, type 2 diabetes and obesity. Both plants and their constituents can reduce fat storage through suppression of adipocyte functions, and support of gut microbiota. In addition, tea can prevent obesity via reduction of appetite, food consumption and food absorption in gastrointestinal system and through the changes in fat metabolism.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shehla Pervin ◽  
Srinivasa T. Reddy ◽  
Rajan Singh

Obesity is a global health problem and a major risk factor for several metabolic conditions including dyslipidemia, diabetes, insulin resistance and cardiovascular diseases. Obesity develops from chronic imbalance between energy intake and energy expenditure. Stimulation of cellular energy burning process has the potential to dissipate excess calories in the form of heat via the activation of uncoupling protein-1 (UCP1) in white and brown adipose tissues. Recent studies have shown that activation of transforming growth factor-β (TGF-β) signaling pathway significantly contributes to the development of obesity, and blockade or inhibition is reported to protect from obesity by promoting white adipose browning and increasing mitochondrial biogenesis. Identification of novel compounds that activate beige/brown adipose characteristics to burn surplus calories and reduce excess storage of fat are actively sought in the fight against obesity. In this review, we present recent developments in our understanding of key modulators of TGF-β signaling pathways including follistatin (FST) and myostatin (MST) in regulating adipose browning and brown adipose mass and activity. While MST is a key ligand for TGF-β family, FST can bind and regulate biological activity of several TGF-β superfamily members including activins, bone morphogenic proteins (BMP) and inhibins. Here, we review the literature supporting the critical roles for FST, MST and other proteins in modulating TGF-β signaling to influence beige and brown adipose characteristics. We further review the potential therapeutic utility of FST for the treatment of obesity and related metabolic disorders.


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