Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects

Andreotti, A. C.; Lanzi, Roberto; Manzoni, M.; Caumo, Andrea; Moreschi, Alexandre Heitor; Pontiroli, Antonio E.

doi:10.1016/0026-0495(94)90212-7

Cited by 39 publications

(26 citation statements)

References 46 publications

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“…This if anything should have enhanced our ability to detect an effect of growth hormone. Higher plasma growth hormone concentrations than those produced in the present experiment can occur in young people particularly around the time of puberty [44] and lower concentrations with obesity or ageing [20,45,46]. Thus, we cannot rule out the possibility that higher and more frequent nocturnal increases in growth hormone than those produced in the present experiments may exert metabolic effects the following morning in some people.…”

Section: Resultscontrasting

confidence: 61%

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

et al. 1998

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Section: Resultscontrasting

confidence: 61%

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

et al. 1998

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“…It has also been shown that the rate of appearance of FFA at night is increased in type 2 diabetics (30) as well as an overnight elevation in plasma FFA that is correlated with the overnight increase in hepatic glucose output in type 2 diabetes (44). In addition, it has been demonstrated that a reduction in overnight FFA levels by acute pharmacological blockade of lipolysis results in a reduction of insulin levels (1). This suggests that the elevated nocturnal FFA observed with fat feeding may be pivotal in the development of hepatic insulin resistance in addition to being a potential signal for insulin upregulation, even when fasting FFA are unchanged.…”

Section: Discussionmentioning

confidence: 99%

Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia

Kim¹,

Catalano²,

Hsu³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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RN. Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia. Am J Physiol Endocrinol Metab 292: E1590 -E1598, 2007. First published January 30, 2007; doi:10.1152/ajpendo.00669.2006.-Obesity is strongly associated with hyperinsulinemia and insulin resistance, both primary risk factors for type 2 diabetes. It has been thought that increased fasting free fatty acids (FFA) may be responsible for the development of insulin resistance during obesity, causing an increase in plasma glucose levels, which would then signal for compensatory hyperinsulinemia. But when obesity is induced by fat feeding in the dog model, there is development of insulin resistance and a marked increase in fasting insulin despite constant fasting FFA and glucose. We examined the 24-h plasma profiles of FFA, glucose, and other hormones to observe any potential longitudinal postprandial or nocturnal alterations that could lead to both insulin resistance and compensatory hyperinsulinemia induced by a high-fat diet in eight normal dogs. We found that after 6 wk of a high-fat, hypercaloric diet, there was development of significant insulin resistance and hyperinsulinemia as well as accumulation of both subcutaneous and visceral fat without a change in either fasting glucose or postprandial glucose. Moreover, although there was no change in fasting FFA, there was a highly significant increase in the nocturnal levels of FFA that occurred as a result of fat feeding. Thus enhanced nocturnal FFA, but not glucose, may be responsible for development of insulin resistance and fasting hyperinsulinemia in the fat-fed dog model. obesity; diurnal IT HAS TRADITIONALLY BEEN BELIEVED that the development of insulin resistance associated with obesity is due to an increase in the level of circulating free fatty acids (FFA) resulting from an impairment of insulin's ability to suppress lipolysis in adipose tissue (4,7,21). Increased FFA levels have been shown to decrease insulin's ability both to suppress hepatic glucose output and to promote peripheral glucose uptake, which can then result in an increase in fasting glucose (14,15). It has traditionally been thought that this increase in fasting glucose resulting from insulin resistance is responsible for compensatory hyperinsulinemia. Thus increasing FFA by lipid infusion results in development of insulin resistance and a compensatory increase in insulin levels (9) in addition to causing mild fasting hyperglycemia due to stimulation of both glycogenolysis and gluconeogenesis (40). However, studies in several different animal models as well as in humans have not consistently demonstrated increases in fasting FFA or glucose during the development of insulin resistance and hyperinsulinemia during obesity (16,20,22,38,41). Studies conducted in our own laboratory (25, 31) using the fat-fed dog model have found development of insulin resistance with concomitant increases of 90 -150% in basal insulin with no significant changes in either fastin...

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“…There is also evidence that FFAs may themselves directly inhibit adipose tissue FFA release (40). In contrast, lowering plasma FFA concentrations decreases glucose-mediated insulin secretion (41) and can increase plasma growth hormone concentrations (42). Therefore, changes in plasma FFA concentrations influence the secretion of lipolytic and antilipolytic hormones in a counterregulatory fashion.…”

Section: Figurementioning

confidence: 99%

Energy expenditure, sex, and endogenous fuel availability in humans

Nielsén¹,

Guo²,

Albu³

et al. 2003

J. Clin. Invest.

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IntroductionApproximately 50% of postabsorptive energy needs in humans are supplied from the oxidation of fatty acids. The major source of this lipid fuel is circulating FFAs that are released from lipolysis of adipose tissue triglyceride. Maintaining normal FFA availability is of considerable importance in human health (1), because high FFA concentrations are associated with a number of cardiovascular risk factors (2) and a predisposition to type 2 diabetes mellitus (3). Experimentally increasing FFA concentrations in normal humans can induce insulin resistance (4), disordered lipoprotein metabolism (5), altered vascular reactivity (6), and abnormal insulin secretion (7).At rest, an average adult with 15 kg of body fat (>50 moles of fatty acids) releases less than 0.4 mmol/min into the circulation to provide energy for fat-free tissue. This is in striking contrast to glucose fuel, where hepatic glycogen stores are approximately 370 mmol and glucose is released at rates of approximately 0.8 mmol/min (8). Understanding the regulation of this relatively massive adipose tissue fuel depot is important given the prevalence of obesity is increasing rapidly in many Western societies.The factors that regulate changes in FFA release in response to changing lipid fuel needs are relatively well described. The insulin secretion stimulated by carbohydrate ingestion markedly inhibits FFA release, thereby suppressing FFA concentrations and fatty acid oxidation by 80-90% (9). In contrast, carbohydrate deprivation or fasting reduces insulin secretion, which enhances adipose tissue FFA release, allowing FFA concentrations to increase by approximately 300% to facilitate greater fat oxidation. Exercise, the most potent physiological stimulus to fat oxidation, can increase FFA release by more than 300% (10), primarily through increased catecholamine stimulation of adipose β-adrenergic receptors. This relatively good understanding of the short-term regulators of FFA release is not mirrored by an equal appreciation of the factors that influence average resting FFA availability.Understanding the normal interaction between adipose tissue fuel release rates and fat-free mass (FFM) fuel use rates is important for understanding the effects of body fat on health. The approach to comparing fuel release rates between groups with different weights and/or different body composition can influence how the information is interpreted, however. For example, there has been controversy regarding whether obesity causes higher FFA concentrations because of greater release or lesser clearance of FFA from the circulation. Obese adults have FFA release rates similar to lean adults, relative to body weight or body fat (11, 12), Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because "normal" FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean a...

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Acute pharmacologic blockade of lipolysis normalizes nocturnal growth hormone levels and pulsatility in obese subjects

Cited by 39 publications

References 46 publications

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia

Energy expenditure, sex, and endogenous fuel availability in humans

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