scholarly journals Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shu Fang ◽  
Yingying Cai ◽  
Fuping Lyu ◽  
Hongbin Zhang ◽  
Chunyan Wu ◽  
...  

Background. The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. Results. The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. Conclusions. Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.

2006 ◽  
Vol 27 (3) ◽  
pp. 370-379 ◽  
Author(s):  
Cameron Rink ◽  
Sashwati Roy ◽  
Savita Khanna ◽  
Trenton Rink ◽  
Debasis Bagchi ◽  
...  

The effects of oral niacin-bound chromium (NBC) supplementation on the subcutaneous fat tissue of type 2 Lepr db obese diabetic mice were examined using high-density comprehensive mouse genome (45,101 probe sets) expression arrays. The influence of such supplementation on the plasma cardiovascular risk factors of these mice was also investigated. Supplementation of NBC had no significant effect on age-dependent weight gain in the Lepr db obese diabetic mice. However, NBC lowered total cholesterol (TC), TC-to-HDL ratio, LDL cholesterol, and triglyceride levels while increasing HDL cholesterol in the blood plasma. No effect of NBC supplementation was observed on fasting blood glucose levels. Oral glucose tolerance test revealed a significantly improved clearance of blood glucose between 1 and 2 h of glucose challenge in NBC-supplemented mice. Unbiased genome-wide interrogation demonstrated that NBC resulted in the upregulation of muscle-specific gene expression in the fat tissue. Genes encoding proteins involved in glycolysis, muscle contraction, muscle metabolism, and muscle development were specifically upregulated in response to NBC supplementation. Genes in the adipose tissue that were downregulated in response to NBC supplementation included cell death-inducing DNA fragmentation factor (CIDEA) and uncoupling protein-1, which represent key components involved in the thermogenic role of brown adipose tissue and tocopherol transfer protein, the primary carrier of α-tocopherol to adipose tissue. The observation that CIDEA-null mice are resistant to obesity and diabetes suggests that the inhibitory role of NBC on CIDEA expression was favorable. Further studies testing the molecular basis of NBC function and long-term outcomes are warranted.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 756
Author(s):  
Paweł A. Kołodziejski ◽  
Ewa Pruszyńska-Oszmałek ◽  
Tatiana Wojciechowicz ◽  
Maciej Sassek ◽  
Natalia Leciejewska ◽  
...  

Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lachlan Van Schaik ◽  
Christine Kettle ◽  
Rodney Green ◽  
Helen R. Irving ◽  
Joseph A. Rathner

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary β-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human in vitro to in vivo models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.


2020 ◽  
Vol 477 (13) ◽  
pp. 2477-2487
Author(s):  
Sarah Justesen ◽  
Kirsten V. Haugegaard ◽  
Jacob B. Hansen ◽  
Harald S. Hansen ◽  
Birgitte Andersen

Exposure to cold alters glucose and lipid metabolism of white and brown adipose tissue via activation of β-adrenergic receptor (ADRB). Fibroblast growth factor 21 (FGF21) has been shown to be locally released from adipose tissue upon activation of ADRBs and FGF21 increases glucose uptake in adipocytes. Therefore, FGF21 may play an autocrine role in inducing glucose uptake after β-adrenergic stimulation. To determine the putative autocrine role of FGF21, we stimulated three different types of adipocytes in vitro with Isoprenaline (Iso), an ADRB agonist, in the presence or absence of the FGF receptor (FGFR) inhibitor PD 173074. The three cell lines represent white (3T3-L1), beige (ME3) and brown (WT-1) adipocyte phenotypes, respectively. All three cells systems expressed β-klotho (KLB) and FGFR1 after differentiation and treatment with recombinant FGF21 increased glucose uptake in 3T3-L1 and WT-1 adipocytes, while no significant effect was observed in ME3. Oppositely, all three cell lines responded to Iso treatment and an increase in glucose uptake and lipolysis were observed. Interestingly, in response to the Iso treatment only the WT-1 adipocytes showed an increase in FGF21 in the medium. This was consistent with the observation that PD 173074 decreased Iso-induced glucose uptake in the WT-1 adipocytes. This suggests that FGF21 plays an autocrine role and increases glucose uptake after β-adrenergic stimulation of cultured brown WT-1 adipocytes.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1479
Author(s):  
Agnieszka Pinkowska ◽  
Marzenna Podhorska-Okołów ◽  
Piotr Dzięgiel ◽  
Katarzyna Nowińska

Irisin (Ir) is an adipomyokine that is involved in the regulation of metabolic processes. It also influences processes related to inflammation, including cancer. Initially, Ir was considered a hormone secreted by skeletal muscles in response to physical exercise. Further studies showed that Ir is also present in other healthy tissues, organs, and plasma. It influences the change in phenotype of white adipose tissue (WAT) into brown adipose tissue (BAT). It increases mitochondrial biogenesis and affects the expression of thermogenin (UCP1). This adipomyokine has also been found in many tumor tissues and in the serum of cancer patients. Studies are underway to determine the association between Ir and carcinogenesis. It has been confirmed that Ir inhibits in vitro proliferation, migration, and invasion. It is involved in the inhibition of epithelial–mesenchymal transition (EMT). Additionally, Ir affects the expression of the transcription factor Snail, which is involved in EMT, and inhibits transcription of the gene encoding E-cadherin, which is characteristic of epithelial-derived cells. Many studies have been performed to determine the role of Ir in physiological and pathological processes. Further detailed studies should determine more precisely the effect of Ir on the body in health and disease.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI

Author(s):  
Aleix Gavaldà-Navarro ◽  
Joan Villarroya ◽  
Rubén Cereijo ◽  
Marta Giralt ◽  
Francesc Villarroya

2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.


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