Oral Presentation Australian & New Zealand Obesity Society 2015 Annual Scientific Meeting

Lower muscle sympathetic nerve activity is associated with liver insulin sensitivity in non-diabetic men with obesity (#97)

Daniel Chen 1 , Rachael Brown 2 3 , Carsten Liess 4 , Ann Poljak 5 6 , Aimin Xu 7 , Herbert Zhang 7 , Michael Trenell 8 , Arthur Jenkins 1 9 , Donald Chisholm 1 , Dorit Samocha-Bonet 1 6 , Jerry Greenfield 1 10
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. School of Medicine, University of Western Sydney, Sydney, Australia
  3. Neuroscience Research Australia, Sydney, Australia
  4. Philips Healthcare, Hamburg, Germany
  5. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia
  6. School of Medical Sciences, University of New South Wales, Sydney, Australia
  7. State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong
  8. MoveLab, Newcastle University, Newcastle, United Kingdom
  9. School of Health Science, University of Wollongong, Wollongong, Australia
  10. Department of Endocrinology and Diabetes Centre, St Vincent's Hospital, Sydney, Australia

Introduction: Muscle sympathetic nervous activity (MSNA) may play a role in insulin resistance in humans. However, the direction and nature of the relationships between MSNA and peripheral or hepatic insulin resistance in obesity remain unclear.

Methods: Forty-five non-diabetic obese subjects (22 men, 23 women) aged 51±11 years were studied. Two-step (low-dose [15] and high-dose [80] mU/m2/min) hyperinsulinaemic-euglycaemic clamps were performed using deuterated glucose to determine liver and muscle insulin sensitivity. Subjects in the top tertile of endogenous glucose production (EGP) suppression were deemed Liversen; those in the bottom two tertiles were deemed Liverres. Subjects in the top tertile of glucose infusion rate (GIR) during the high-dose insulin clamp were deemed Musclesen; the bottom two tertiles were deemed Muscleres. Clinical and metabolic parameters were assessed. MSNA was measured by microneurography and abdominal fat distribution and liver lipid by magnetic resonance imaging.

Results: MSNA did not differ between insulin-sensitive and insulin-resistantgroups stratified by either liver or muscle insulin sensitivity. However, insulin-sensitive men had lower MSNA burst frequency compared with their insulin-resistant counterparts (27±14 vs. 38±7 bursts per minute; P=0.03, Liversen and Liverres,respectively; and 24±9 vs. 38±9 burst per minute; P=0.004, Musclesen and Muscleres, respectively).  No differences in MSNA were observed in women. In men, MSNA burst frequency correlated inversely with liver insulin sensitivity (r=-0.53, P=0.02) and fibroblast growth factor (FGF)-19 (r=-0.47, P=0.03) and positively with C-reactive protein (CRP) (r=0.57, P=0.006).

Conclusions: Basal sympathetic nerve activity is related to liver insulin sensitivity in men.  MSNA is significantly associated with circulating hepatokines, suggesting a potential hepato-endocrine-autonomic axis. Future studies are needed to clarify the influence of sympathetic nervous activity on liver insulin sensitivity in men.