Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement

Ahmad, Aftab; Guzder, Rustom; Wallace, Andrew M.; Thomas, Joegi; Fraser, William D.; Vora, Jiten

doi:10.1210/jcem.86.8.7716

Cited by 27 publications

(25 citation statements)

References 56 publications

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“…Previous studies have demonstrated relatedness of leptin to luteinizing hormone, cortisol, and GH (3,20,21), suggesting that leptin may be an important regulator of neuroendocrine function. In this regard, studies of Chehab et al (10) and Ahima et al (1) have shown that leptin acts as a hormonal signal that conveys biological information from fat tissue to the reproductive axis and that leptin treatment accelerates the onset of puberty.…”

Section: Discussionmentioning

confidence: 95%

“…Plasma leptin levels are inversely related to those of ACTH in young men (20) and display pattern synchrony with those of luteinizing hormone and estradiol in young women (21). In addition, leptin is related to growth hormone (GH), and GH replacement may increase leptin pulsatility (3,31). Furthermore, insulin has been implicated in the physiological regulation of leptin independently of changes in body composition (16,33).…”

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confidence: 99%

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Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin

Koutkia¹,

Canavan²,

Johnson³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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To investigate the regulation of leptin secretion and pulsatility by fat mass, we performed overnight leptin sampling every 20 min for 12 h and compared leptin dynamics with total body and regional fat measurements in 20 healthy male subjects. Simultaneous growth hormone (GH), cortisol, and insulin levels were assessed to determine relatedness and synchronicity during overnight fasting. Deconvolution analyses were performed to determine simultaneous hormonal dynamics, synchronicity, and interrelatedness using cross-correlation and cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 4.7 Ϯ 0.4 leptin pulses/12 h. Leptin secretion correlated highly with total body fat (r ϭ 0.78, P Ͻ 0.001) and regional fat depots. In contrast, leptin pulsatility did not correlate with total fat (r ϭ 0.07, P ϭ 0.785) or other measures of fat. There was synchronicity between GH and leptin (lag Ϫ39 minutes), cortisol and leptin (lag Ϫ211 min), and leptin and insulin, with leptin following insulin by 275 min. The mean random X-ApEn was significant between leptin and GH (0.854 Ϯ 0.030), cortisol (0.891 Ϯ 0.023), and insulin (0.868 Ϯ 0.034), demonstrating a high degree of regularity and pattern frequency. These data demonstrate differential regulation of leptin secretion and pulsatility in adipocytes and suggest that the leptin pulse generator is extrinsic to fat, whereas fat mass acts as an amplifier to modulate secretion and amplitude for a given pulsatility. We demonstrate synchronicity between leptin and GH, cortisol, and insulin. The directionality of the cross correlation suggests a temporal construct in which changes in leptin follow those of insulin but precede those of GH and cortisol during overnight fasting. subcutaneous fat; abdominal fat; synchronicity; pulsatility; cross-approximate entropy LEPTIN, AN ADIPOCYTE-DERIVED HORMONE, has been implicated in the regulation of food intake, metabolism, and neuroendocrine function (2, 39). Circulating leptin concentrations are highly correlated to weight and body fat in animals and humans (39), suggesting that leptin is an important component of a complex neuroendocrine signaling system to sense and effect changes in overall nutritional status (2). For example, leptin deficiency (undernutrition) results in hyperphagia and reduced energy metabolism, whereas leptin excess (overnutrition) results in hypophagia and increased energy metabolism (14). Moreover, nutritionally mediated changes in leptin significantly affect neuroendocrine function. Leptin administration blunts food deprivation-induced hypercortisolemia, hypothyroidism, and hypogonadism in animals (2). Plasma leptin levels are inversely related to those of ACTH in young men (20) and display pattern synchrony with those of luteinizing hormone and estradiol in young women (21). In addition, leptin is related to growth hormone (GH), and GH replacement may increase leptin pulsatility (3, 31). Furthermore, insulin has been implicated in the physiological regulation of leptin independently of changes in body compositio...

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin

Koutkia¹,

Canavan²,

Johnson³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…In the whole dataset, 24-h leptin levels were the principal correlates of 24-h GH levels and they changed consensually following weight loss. Several authors 35,36 have reported that GH supplementation in GH-deficient adult patients decreased both body fat and plasma leptin concentrations. Moreover, Isokazi et al 37 showed in Zucker fa/fa rats that GH directly inhibits leptin gene expression in visceral fat tissue.…”

Section: Discussionmentioning

confidence: 99%

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

et al. 2008

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Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m 2 ) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m 2 ), sex-and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35±4 kg (or 26 ± 2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290 ± 31 vs 88 ± 4 pmol l À1 , P ¼ 0.0002), insulin resistant (23.5±2.8 vs 52.9±4.9 mmol min À1 kg FFM À1 , P ¼ 0.0006) and hyperleptinaemic (52.5±5.8 vs 10.9±3 ng ml À1 , P ¼ 0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02 ± 0.18 vs 1.09 ± 0.19 mU ml À1 of controls, P ¼ 0.01), whereas serum GH levels were suppressed (0.46±0.10 vs 3.01±1.15, P ¼ 0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4±2.7 ng ml À1 , P ¼ 0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.

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“…Leptin secretion may have an Integrative physiology of human adipose tissue KN Frayn et al ultradian pattern 160,161 and show pulsatility with a periodicity of less than 1 h. 162 For such leptin pulsation, it has been suggested that growth hormone pulsation is the pacemaker, 163 but this remains to be proven. Systemic plasma NEFA and glycerol concentrations show pulsatility, 164 as does lipolysis in omental adipose tissue in dogs, arguing for coordinated action of adipose tissue throughout the body.…”

Section: Pulsatilitymentioning

confidence: 99%

Integrative physiology of human adipose tissue

et al. 2003

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Adipose tissue is now recognised as a highly active metabolic and endocrine organ. Great strides have been made in uncovering the multiple functions of the adipocyte in cellular and molecular detail, but it is essential to remember that adipose tissue normally operates as a structured whole. Its functions are regulated by multiple external influences such as autonomic nervous system activity, the rate of blood flow and the delivery of a complex mix of substrates and hormones in the plasma. Attempting to understand how all these factors converge and regulate adipose tissue function is a prime example of integrative physiology. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities, including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissues to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. This implies the existence of one (or more) signal(s) to the adipose tissue that reflects the body's energy status, and points once again to the need for an integrative view of adipose tissue function.

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Circadian and Ultradian Rhythm and Leptin Pulsatility in Adult GH Deficiency: Effects of GH Replacement

Cited by 27 publications

References 56 publications

Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin

Characterization of leptin pulse dynamics and relationship to fat mass, growth hormone, cortisol, and insulin

Daylong pituitary hormones in morbid obesity: effects of bariatric surgery

Integrative physiology of human adipose tissue

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