Kai Henrik Wiborg Lange

The effect of recombinant human growth hormone and resistance training on IGF‐I mRNA expression in the muscles of elderly men

The expression of two isoforms of insulin‐like growth factor‐I (IGF‐I): mechano growth factor (MGF) and IGF‐IEa were studied in muscle in response to growth hormone (GH) administration with and without resistance training in healthy elderly men. A third isoform, IGF‐IEb was also investigated in response to resistance training only. The subjects (age 74 ± 1 years, mean ±S.E.M) were assigned to either resistance training with placebo, resistance training combined with GH administration or GH administration alone. Real‐time quantitative RT‐PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline, after 5 and 12 weeks in the three groups. GH administration did not change MGF mRNA at 5 weeks, but significantly increased IGF‐IEa mRNA (237%). After 12 weeks, MGF mRNA was significantly increased (80%) compared to baseline. Five weeks of resistance training significantly increased the mRNA expression of MGF (163%), IGF‐IEa (68%) and IGF‐IEb (75%). No further changes were observed after 12 weeks. However, after 5 weeks of training combined with GH treatment, MGF mRNA increased significantly (456%) and IGF‐IEa mRNA by (167%). No further significant changes were noted at 12 weeks. The data suggest that when mechanical loading in the form of resistance training is combined with GH, MGF mRNA levels are enhanced. This may reflect an overall up‐regulation of transcription of the IGF‐I gene prior to splicing.

GH administration and discontinuation in healthy elderly men: effects on body composition, GH-related serum markers, resting heart rate and resting oxygen uptake

BACKGROUND AND OBJECTIVES GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF‐I axis. Several studies have focused on effects of GH administration in the elderly in the last decade. However, very limited information is available regarding changes in body composition and EE upon GH discontinuation in the elderly. The present study therefore investigated the effects of 12u2003weeks of GH administration and subsequent discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men.

Fat metabolism in exercise – with special reference to training and growth hormone administration

Despite abundance of fat, exclusive dependency on fat oxidation can only sustain a metabolic rate corresponding to 50–60% of VO2max in humans. This puzzling finding has been subject to intense research for many years. Lately, it has gained renewed interest as a consequence of increased obesity and physical inactivity imposed by Western lifestyle. Why are humans so poor at metabolizing fat? Can fat metabolism be manipulated by exercise, training, diet and hormones? And why is fat stored in specialized adipose tissue and not just as lipid droplets inside muscle cells?

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well‐trained males (age 25 ± 2 years (mean ±s.e.m.); peak oxygen consumption : 62 ± 1 ml min−1 kg−1 (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an ∼60‐fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.

Subcutaneous Abdominal Adipose Tissue Lipolysis During Exercise Determined by Arteriovenous Measurements in Older Women

OBJECTIVESnTo characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise.nnnDESIGNnCross-sectional exercise study.nnnSETTINGnExercise laboratory, Copenhagen, Denmark.nnnPARTICIPANTSnSeven healthy, older women (mean age +/- standard error = 75 +/- 2 years); weight: 67.8 +/- 4.9 kg; body fat: 40 +/- 3; maximal oxygen uptake (VO2max): 1.43 +/- 0.07 L.min 1).nnnMEASUREMENTSnBody composition (dual energy x-ray absorptiometry (DEXA)), maximal oxygen uptake (VO2max, maximal cycling test), lipolytic response to exercise (arterial and adipose tissue venous catheterization at rest and during 60 minutes of continuous cycling at a load corresponding to 60 of VO2max), adipose tissue blood flow (ATBF) (133Xenon (133Xe) washout), oxygen consumption and respiratory exchange ratio during exercise (indirect calorimetry), whole blood glycerol, plasma nonesterified fatty acids (NEFA), lactate, glucose, epinephrine, norepinephrine, insulin, serum growth hormone, and hematocrit.nnnRESULTSnGlycerol and NEFA mobilization rates increased by 250 and 180, respectively, from rest to exercise. This was achieved primarily by an increase in veno-arterial differences, because ATBF did not increase significantly. NEFA:glycerol mobilization ratio was about two at rest and remained at that level during exercise, indicating significant local reesterification in both conditions. After an initial decrease, arterial plasma NEFA concentration increased significantly, by 26, indicating that NEFA delivery exceeded muscle uptake.nnnCONCLUSIONSnOlder women are capable of prompt and substantial increase in subcutaneous abdominal adipose tissue glycerol and NEFA mobilization rates in response to moderate acute endurance exercise. The lipolytic response matches skeletal muscle NEFA uptake, and decreased ability to mobilize fat during exercise is therefore not likely to cause increased fat mass with advancing age.

Adrenergic Regulation of Energy Metabolism

During exercise, energy turnover increases and adrenergic mechanisms play an important role in this regulation. In addition, increased adrenergic activity during exercise also results in an increased heart rate and in an enhanced force of myocardial contraction as well as in vasoconstriction in the splanchnic circulation, in the kidneys, and in noncontracting muscles. These circulatory changes favor a redistribution of blood flow to exercising muscle as well as an increased cardiac output (Rowell. Human circulation regulation during physical stress. Oxford University Press, New York, 1986). Furthermore, the adrenergic activity stimulates sweat glands and thereby influences thermoregulation, and it causes an increased contractility of skeletal muscle as well as influences exercise-induced suppression of components of the human immune system. In the present chapter, it is demonstrated how adrenergic activity can influence substrate mobilization and utilization both directly and indirectly via secretion of hormones.