Plenary 3. Wed 02 June – Talk 1, Juleen R. Zierath

Exercise, inactivity, and circadian rhythms – re-setting the clock in metabolic disease: Juleen Zierath, Stockholm, Sweden

The rise of cardiometabolic disease as global health threat: towards the UN 2030 goals

Juleen R. Zierath is Professor of Experimental Physiology and leads the Section of Integrative Physiology, Department of Molecular Medicine and Surgery at Karolinska Institutet, Stockholm, Sweden. She is also Professor of Integrative Physiology and Executive Director at Novo Nordisk Foundation Center for Basic Metabolic Research at University of Copenhagen, Denmark. She obtained her B.Sc. from UWRF in 1984, a M.A. from Ball State University in 1986, and a Ph.D. from Karolinska Institutet in 1995. Her research focuses on the development of insulin resistance in type 2 diabetes mellitus. In 2006 she was appointed to the Nobel Assembly at Karolinska Institutet and since 2008 she has been a member of the Nobel Committee for Physiology and Medicine. She is currently a board member of Nobel Media and Keystone Symposia, and a member of Academia Europaea and the Royal Swedish Academy. She has received several awards, including the Minkowski Prize from the European Association for the Study of Diabetes, the Datta Lectureship Award from the Federation of European Biochemical Society, the Nordic Medicine Prize for Research in Diabetes from the Foundation for the Nordic Medicine, and in 2019, she received an Honorary Doctor of Science Degree from UWRF.

Accumulating evidence supports the role of the circadian clock in regulating metabolism.  Both mitochondrial oxidative capacity and lipolysis show circadian patterns in humans, and disruption of these may be implicated in the pathogenesis of metabolic disease. Thus time-targeted lifestyle strategies may offer therapeutic potential.

Understanding how circadian rhythm affects the beneficial effects of exercise, and how best to modify exercise type, intensity and modality so as to optimise metabolic outcomes, are critical.  Disrupted chronobiology is a key factor contributing to hyperglycemia and hypertriglyceridemia associated with diabetes. Studies suggest that exercising in the evening may provide the most benefit for postprandial glycemia, as well as enhancing insulin sensitivity during the nocturnal period and lowering fasting plasma glucose levels in the morning.  The underlying mechanisms of this benefit of evening exercise compared with exercise at other times may involve changes in melatonin signalling, as well as improvement in hepatic insulin sensitivity, although further study is needed.

Investigating the link between chronobiology, exercise, and energy metabolism in metabolic disease is clearly relevant with the escalating global obesity epidemic.  Future research should be directed to understanding the acute and long-term metabolic impact of aerobic and resistance exercise, as well as their combination. As for pharmacotherapeutic approaches, optimising the timing of exercise will offer the possibility of improved outcome in individuals with metabolic disease.

Recent references

Hawley JA, Sassone-Corsi P, Zierath JR. Chrono-nutrition for the prevention and treatment of obesity and type 2 diabetes: from mice to men. Diabetologia 2020;63:2253-9.

Sardon Puig L, Pillon NJ, Näslund E, Krook A, Zierath JR. Influence of obesity, weight loss, and free fatty acids on skeletal muscle clock gene expression. Am J Physiol Endocrinol Metab 2020;318:E1-E10.

Altıntaş A, Laker RC, Garde C, Barrès R, Zierath JR. Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development. Epigenomics 2020;12:701-13.

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