Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the long-chain fatty acid oleate (150 nmol/min, 24 h), the medium-chain fatty acid caprylate, or the solvent. Corticosterone (Cort) and norepinephrine (NE) were measured as indexes for HPA axis and sympathetic activity, respectively. Insulin sensitivity was assessed by means of an intravenous glucose tolerance test (IVGTT). Oleate infusion induced increases in plasma Cort (Δ = 13.5 ± 3.6 µg/dl; P < 0.05) and NE (Δ = 235 ± 76 ng/l; P < 0.05), whereas caprylate and solvent had no effect. The area under the insulin response curve to the IVGTT was larger in the oleate-treated group than in the caprylate and solvent groups (area = 220 ± 35 vs. 112 ± 13 and 106 ± 8, respectively, P < 0.05). The area under the glucose response curves was comparable [area = 121 ± 13 (oleate) vs. 135 ± 20 (caprylate) and 96 ± 11 (solvent)]. The results are consistent with the concept that increased portal free fatty acid is involved in the induction of visceral obesity-related insulin resistance via activation of the HPA axis and sympathetic system.

Forced and voluntary exercise counteract insulin resistance in rats:The role of coping style

There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGITs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style. (C) 2012 Elsevier Inc. All rights reserved

Sympatho-adrenal regulation of energy metabolism. A study in swimming rats

The role of the sympatho-adrenal system in energy metabolism during exercise has been studied extensively for the last decades. Experiments with chemical and electrical stimulation of the sympatho-adrenal system have yielded considerable insight into the control of circulating glucose and free fatty acid (FFA) concentrations. Most studies, however, were focussed on the levels of nutrients and their regulatory hormones, rather than on the utilization of these nutrients. ... Zie: Summary.

Study of the Residual Linewidth of the Level-Anti-Crossing Signal in p-Benzoquinone

The linewidth of the level-anti-crossing (LAC) signal in p-benzoquinone has been examined using optical detection of magnetic resonance between states in the avoided crossing region. The results are used to separate the homogeneous (due to hyperfine coupling) from the inhomogeneous (due to disorder) contribution to the LAC linewidth.

Individual variation in the (patho)physiology of energy balance

There are large individual differences in the susceptibility for metabolic disorders such as obesity, the metabolic syndrome and type 2 diabetes. Unfortunately, most animal studies in this field ignore the importance of individual variation which limits the face validity of these studies for translation to the human situation. We have performed a series of studies that were particularly focused on the individual differences in the (patho)physiology of energy balance. The studies were performed with passive and proactive individuals of two different rat strains: the Roman High and Low Avoidance rats and the Wild type Groningen rat. The data reveal that passive and proactive individuals differ significantly on several parameters, i.e. body composition, Hypothalamic–Pituitary–Adrenal (HPA) axis activity, plasma levels of insulin and leptin, intestinal transit time, systolic blood pressure and meal patterns. We also found that the selection line of the Roman Low Avoidance rat may be considered as a non-obese animal model for the metabolic syndrome, since these rats display, under sedentary conditions, many of the related symptoms such as hypertension, visceral adiposity and insulin resistance during an intravenous glucose tolerance test. These symptoms disappeared when the animals were allowed to exercise voluntarily in a running wheel. We conclude that experiments with passive and proactive individuals are highly relevant for studying the (patho)physiology and behavior of energy balance and the related metabolic disorders.

Pharmacological treatment of hyperinsulineamia in rats depends on coping style

Passive and proactive coping styles are associated with marked differences in behavioral and neuroendocrine responses. Previous studies revealed that the passive individuals are more prone to hyperinsulineamia. Likewise, we hypothesize that different coping styles may require different drugs to treat this. We tested this by treating passive and proactive rats (Roman Low Avoidance and Roman High Avoidance rats respectively) with either Rosiglitazone or with RU486. After eight days of treatment we performed and intravenous glucose tolerance test (IVGTT) and we compared the insulin and glucose levels with those measured during the IVGTT at baseline. Rosiglitazone improved insulin levels during an IVGTT in both passive and proactive coping styles. RU486, however, lowered insulin levels only in rats with a passive coping style. This study suggests that insight in the neuroendocrine differences between passive and proactive coping styles may provide an extra impulse to improve treatment of insulin resistance, since it allows the application of drugs targeted at the individual.

Coping style predicts the (in)sensitivity for developing hyperinsulinemia on a high fat diet in rats

The aim of this study was to explore interactions between coping style and diet as risk factors for developing insulin resistance in rats. We hypothesized that rats characterized by a passive coping strategy are more susceptible for developing insulin resistance and visceral obesity than proactively coping rats, particularly on a high (45%) fat diet. This hypothesis was tested by comparing 1) insulin and glucose responses to an intravenous glucose tolerance test (IVGTT), and 2) body fat distribution, in two rat models for passive and proactive coping styles. We found that the most extremely passive rats are characterized by elevated insulin levels during a IVGTT, even on chow. Moderately passive rats display normal insulin responses under chow conditions, but develop insulin resistance on a high fat diet. Proactive rats are remarkably resistant to insulin resistance and visceral obesity, even when overfeeding on a high fat diet. Carcass analysis revealed that passive rats are characterized by increased epididymal fat deposition, which is in line with the observed differences in insulin resistance. We conclude that a passive personality is prone to develop insulin resistance and visceral obesity on a palatable fat diet and a proactive personality might be protected against the development of diet-induced insulin resistance.

Neuroendocrinology of insulin resistance: metabolic and endocrine aspects of adiposity

Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly attenuating peripheral insulin signaling, glucocorticoids oppose the activity of central nervous regulatory systems that stimulate insulin action. Among the factors that promote insulin action is leptin. Leptin regulates peripheral fuel partitioning and insulin action mainly through hypothalamic neuronal networks, which in turn, regulate endocrine activity of adipose tissue in a way comparable to thiazolidinediones. These are a class of insulin-sensitizing drugs, which exert their antidiabetic effects through the gamma isoform of peroxisome proliferator-activated receptor (PPAR-γ). Since glucocorticoids oppose leptin action at several levels of control (including the central nervous system, CNS), it is argued that subjects easily develop obesity and associated metabolic disorders.