Physical activity and exercise in the regulation of adipose mass and function Key Questions What is the impact of exercise on adipose and fat metabolism? To what extent does exercise and physical activity change adipose tissue masses? What is the impact of chronic exercise (training) on adipose tissue function - independent of energy balance? Professor Dylan Thompson Department for Health University of Bath d.thompson@bath.ac.uk @DrDylanThompson Fat mobilisation from adipose during exercise Fatty Acid Trafficking Frayn & Coppack (21) In: Adipose Tissue Protocols Springer Thompson et al (212) Physiol Rev. 92: 157-191 Substrate utilisation during Exercise FFA Other Fat Plasma Glucose Muscle Glycogen Intensity (W max ) Exercise Absolute 2 15 1 5 75 75 55 (25 VO2 max; ~6 kcal/min) 55 5 Lower Intensity Exercise 25 4 Absolute Contribution to EE (kcal/min) 1 4 Relative Contribution to EE () Relative Al Mulla et al (2) J. Physiol. 524: 919-928 Intensity (W max ) 6 min exercise = ~3 g fat from AT Van Loon et al (21) J. Physiol. 536(1): 295-34 Romijn et al (1993) Am. J. Physiol. 265: E38-E391 1
Summary 1 At most intensities, fat mobilized from subcutaneous adipose provides much of the energy for exercise At low intensities, FFA from adipose contributes ~9 to energy expenditure Impact of supervised exercise interventions on adipose masses and depots Diet -1 kcal/d Exercise Interventions Exercise 5 d/wk, 6 min Diet -7 kcal/d Exercise +7 kcal/d Change in Mass (kg) -5-1 Weight SCAT VAT Weight SCAT VAT Change in Mass (kg) -2-4 -6 Weight SCAT VAT Weight SCAT VAT Exercise: A preferential effect on visceral adipose tissue? -15-8 16 weeks 16 weeks Ross et al. (1996) J. Appl. Physiol. 81: 2445-2455 Ross et al. (2) Ann. Int. Med. 133:92-13 VAT & Exercise: Meta Analysis The principal finding of this review is that there is no compelling evidence of a weight loss intervention that targets visceral fat preferentially. Rather, it appears that preferential loss of visceral fat is associated with modest weight loss and the effect reduced with greater weight loss Verheggen et al (216) Obesity Reviews 17: 664-69 2
Summary 2 Supervised exercise alongside a controlled diet can lead to quantitatively important reductions in fat mass Fat will be lost from all adipose depots What about exercise in the real world? VAT shows the greatest relative change but the greatest absolute change will be in SCAT mass August 29 Intervention Studies? Systematic Reviews Our results show that isolated aerobic exercise is not an effective weight loss therapy. Isolated aerobic exercise provides modest benefits to blood pressure and lipid levels and may still be an effective weight loss therapy in conjunction with diets. Thorogood et al (211) Am J. Medicine 124(8)747-755 3
Intervention Studies? Systematic Reviews Is this because of poor compliance or compensatory changes in other physical activity? Average weight loss of subjects completing a minimum 1-year weight-management intervention; based on review of 8 studies (N=26,455; 18,199 completers [69]). Franz et al (27) Journal of the American Dietetic Association, 17(1) 1755 1767 Turner et al. (21) Am J Clin Nutr 92:19-116 Regular exercise and energy balance Regular exercise and energy balance Weight loss was ~5 predicted Potential energy deficit reduced by ~1 kcal/d (because of a compensatory ñ in EI) ~ 1 TEE Turner et al. (21) Am J Clin Nutr 92:19-116 Turner et al. (21) Am J Clin Nutr 92:19-116 Summary 3 Real world exercise interventions have a rather modest impact on weight (fat) loss in part because of counter forces such dietary compensation August 29 4
Perspectives kcal/d 1 5 M T W T F S S 15 minutes = 2 of a waking week NEAT NEAT Monday below 6 kcal/min comes from NEFA mobilised from adipose then = 774 kcal/d (~11 g of fat) Tuesday (NB above rest) Tuesday TEE = 28 kcal/d RMR = 166 kcal/d PAEE = 86 kcal/d PAL = 1.69 If 9 of the energy cost of physical activity Monday Wednesday TEE = 28 kcal/d RMR = 166 kcal/d PAEE = 86 kcal/d PAL = 1.69 Thursday Wednesday Thursday Friday Friday Saturday Saturday Sunday Sunday >5, kcal per year! Assumptions, assumptions What contributes to NEAT? 5 Energy Expenditure (kcal/d) >7kg (11 stone) fat (adipose) 4 DIT Levine et al. (26) Arterioscler Thromb Vasc Biol;26:729-736 PAEE BMR 3 2 1 1 2 3 4 5 6 7 8 9 1111213141516181922122232425262728293313233343536373839441424344454647484955152535455565758596 Ninety Middle-aged Men (Rank Order for TEE) Thompson et al (29) Plos ONE 4(2): p. e4337 5
Summary 4 Overall physical activity energy expenditure is incredibly important for energy and fat balance Other effects from exercise? Acute exercise affects adipose tissue Thompson et al (212) Physiol Rev. 92: 157-191 Relative Gene Expression 2.5 2. 1.5 1..5. Adiponectin AMPK 6 min of moderate intensity exercise GLUT4 HSL IRS2 MCP1 PDK4 PGC1a PPARgamma SREBP1c AKT1 ATGL Chen et al (217) Am. J. Physiol. 313: E84-E93 Acute exercise affects adipose tissue Relative Gene Expression 2.5 2. 1.5 1..5. 6 min of moderate intensity exercise # # # # # # Adiponectin AMPK GLUT4 HSL IRS2 MCP1 PDK4 PGC1a PPARgamma SREBP1c AKT1 ATGL Chen et al (217) Am. J. Physiol. 313: E84-E93 Exercise increases markers of angiogenesis in adipose Van Pelt et al (Online First) J. Appl. Physiol. 6
Exercise-induced release of adipokines (IL-6) Acute effects in other tissues? Exercise Lyngso et al (22) J. Physiol. 543.1: 373-378 Hojbjerre et al (27) Eur J Endocrin. 157: 613-623 Chronic exercise-induced changes in adipose tissue Chronic exercise (training) increases adipose sensitivity 256 transcripts differentially affected by exercise 2-3 sessions per week no weight loss 4 months, 5d/wk, weight loss = 1.9kg de Glisezinski et al (23) Am J. Physiol. 285: E984-E99 4 months, 5d/wk, weight loss = 3kg Moro et al (25) MSSE 37(7):1126-1132 (CCL5) Chronic exercise and adipose inflammation No change in BMI Summary 4 Exercise causes acute physiological changes in adipose tissue Chronic exercise (training) improves adipose tissue physiology and function (e.g., improved sensitivity, lower inflammation) Are exercise-induced effects dependent on (modest) changes to energy balance? Baturcam et al (214) Mediators of Inflamm. doi: 1.1155/214/62715 7
Impact of exercise on adipose without weight (fat) loss Energy surplus with and without exercise Impact of exercise on response to overfeeding + 5 + 5 EX EI EE 4 max EI EE 4 max Normal SUR Normal SUR+EX Group 1 Group 2 Walhin et al (213) J. Physiol. 591(24)6231-43 Exercise maintained postprandial insulinaemia and glucose control Exercise maintained adipose gene expression (even during adipose expansion) ~17, Extra kcal Walhin et al (213) J. Physiol. 591(24)6231-43 Walhin et al (213) J. Physiol. 591(24)6231-43 8
Summary 5 Other forms of exercise and overfeeding? Daily vigorous intensity exercise protects against the deleterious effects of an energy surplus Even in the tissue where excess energy is being actively stored (i.e., adipose) Insulin Response to OGTT ( Δ iauc ) 3 2 1 SUR SUR+ ACE SUR+ MOD SUR+ BREAKs Key Questions What is the impact of exercise on adipose and fat metabolism? To what extent does exercise and physical activity change adipose tissue masses? What is the impact of chronic exercise (training) on adipose tissue function - independent of energy balance? James Betts Yung-Chih (Stanley) Chen Javier Gonzalez Will Trim James Turner Jean-Philippe Wahlin Keith Frayn (Oxford) Fredrik Karpe (Oxford) Max Lafontan (Toulouse) Anne Bouloumie (Toulouse) Acknowledgements 9