Effects of amylin on food intake and body weight via sympathetic innervation of the interscapular brown adipose tissue

ABSTRACT

Objective: Amylin acts on the lateral dorsal tegmental nucleus (LDT), resulting in anorexic and weight-loss effects and activates thermogenesis in the interscapular brown adipose tissue (IBAT). In addition, it induces neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT)-mediated feeding. However, the influence of the intact sympathetic nervous system (SNS) in mediating amylin’s effects has not been fully characterised. We investigated whether extracellular signal-regulated kinase (ERK), nNOS, and ChAT activities in the LDT are responsible for amylin’s anorexigenic effects and whether this requires an intact SNS.

Methods: C57BL/6J mice [wild-type (WT), sham, and sympathetic denervation of IBAT] were used. Food consumption, body weight, and distribution of pERK, nNOS, and ChAT positive neurons in the brain were examined following acute and chronic amylin administration.

Results: Food intake was significantly decreased in WT and sham animals following acute amylin injection, but not in the denervated mice. Chronic amylin reduced body weight and serum glucose levels after 6 weeks, but increased insulin levels; no changes were observed in the denervated mice. Acute amylin increased the expression of nNOS, ChAT, and uncoupling protein-1 in the IBAT of WT and sham mice, while no changes were observed in the denervated mice and pERK from the above effect.

Conclusions: Intact SNS of IBAT influences amylin-induced suppression of food intake and body weight, thus affecting nNOS and ChAT signalling in the LDT and locus coeruleus.

KEYWORDS:

• Amylin
• lateral dorsal tegmental nucleus
• interscapular brown adipose tissue
• food intake
• body weight
• sympathetic nervous system

Acknowledgements

K.F., Q.L. and D.P. designed and oversaw the study, data collection, and analysis and drafted the manuscript. H.L., P.L. and R.H contributed to the study design and data analysis C.D. is the guarantor of this work and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors critically reviewed and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (31660701); and the Natural Science Foundation of Inner Mongolia (2018MS0323).

Notes on contributors

Kuikui Fan

Kuikui Fan, Graduate Student, Inner Mongolia Agricultural University. His research aims to understand how effects of amylin administration on metabolic behaviour of mice.

Qiang Li

Qiang Li, Graduate Student, Inner Mongolia Agricultural University. His research focuses on effect of amylin on steroidogenic regulatory factors in central nervous system of mouse.

Deng Pan

Deng Pan, Graduate Student, Inner Mongolia Agricultural University. His research focuses on understanding the response of the expression of oxytocin neurons to ghrelin in mice.

Haodong Liu

Haodong Liu is a postgraduate at the Inner Mongolia Agricultural University.

Penghui Li

Penghui Li is a postgraduate at the Inner Mongolia Agricultural University.

Rihan Hai

Rihan Hai is a teacher at the Vocational and Technical College, Inner Mongolia Agricultural University.

Chenguang Du

Chenguang Du is professor at the college of Veterinary Medicine, Inner Mongolia Agricultural University and corresponding author.