Dataset Information

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

ABSTRACT:

Objective

Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study.

Methods

Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks.

Results

When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)-treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNF?, IL-1?, cyclooxygenase-2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF-?B induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP-dependent protein kinase (PKA) activation inhibitor.

Conclusions

ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.

SUBMITTER: Dai HB

PROVIDER: S-EPMC7821304 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

Dai Hang-Bing HB Wang Fang-Zheng FZ Kang Ying Y Sun Jing J Zhou Hong H Gao Qing Q Li Zhen-Zhen ZZ Qian Pei P Zhu Guo-Qing GQ Zhou Ye-Bo YB

Obesity (Silver Spring, Md.) 20200928 1

<h4>Objective</h4>Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study.<h4>Methods</h4>Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks.<h4>Result ...[more]

PMID: 32985779

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Project description:The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p < 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p< 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.

Dataset Information

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

Objective

Methods

Results

Conclusions

Publications

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

Similar Datasets

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