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Biomedical subjects

G Frühbeck

Publications and source records attributed to G Frühbeck.

At least 37 records · Page 2Linked to original sources

Interactions between leptin and NPY affecting lipid mobilization in adipose tissue.

Lipid turnover and deposition is under the control of developmental, nutritional, metabolic and neuroendocrine influences. The aim of the current investigations was focused on the study of the involvement of leptin and neuropeptide Y in lipid mobilization. The lipolytic rate was assessed through glycerol release after incubation with leptin and NPY at concentrations ranging from 10(-6) to 10(-12) M in isolated adipocytes obtained from female rats. The presence of leptin at concentrations of 10(-12) to 10(-7) M in the incubation medium of isolated fat cells significantly increased (p < 0.0001) glycerol release, except at the concentration of 10(-11) M, where the increase was (p < 0.01) as compared to the basal lipolytic activity. On the other hand, isolated fat cells of Wistar rats bathed in 10(-10) to 10(-6) M concentrations of NPY demonstrated a statistically significant decrease (p < 0.0001) in glycerol release. At equimolar concentrations of leptin and NPY (10(-12) to 10(-6) M) the observed lipolytic activity is comparable to the basal lipolytic activity, except at a concentration of 10(-9) M where upon a significant increase in lipolysis is observed. A further increase in the equimolar concentrations, beyond 10(-9) M results in a return to the basal lipolytic activity. Summing up, new evidence suggests that NPY and leptin may interact in a homeostatic loop to regulate body-fat mass and energy balance not only at the central nervous system level, but also directly at the adipocyte level.

Adipocytes↗

Leptin, but not a beta 3-adrenergic agonist, upregulates muscle uncoupling protein-3 messenger RNA expression: short-term thermogenic interactions.

The short-term effects of leptin and a beta 3-adrenoceptor agonist on thermogenesis and expression of uncoupling proteins (UCPs) in brown adipose tissue (BAT) and muscle and their possible interactions were assessed. One hour after administration of the beta 3-adrenoceptor agonist Trecadrine, a statistically significant increase in UCP1 messenger RNA (mRNA) expression in BAT was observed, whereas UCP2 and UCP3 in both BAT and gastrocnemius muscle were unaffected. Leptin induced an upregulation of UCP3 mRNA in muscle, with no changes in BAT UCP1 mRNA. A statistical interaction was found between leptin and Trecadrine in rectal temperature. The present study provides evidence, for the first time, of the induction of UCP3 mRNA expression in skeletal muscle by leptin in nongenetically obese animals.

Adipose Tissue, Brown↗

Hormone-related, muscle-specific changes in protein metabolism and fiber type profile after faba bean intake.

Male growing Wistar rats were fed, over 15 days, isoenergetic (16.72 +/- 0.49 MJ) and isoproteic (11%) diets containing either lactalbumin or raw Vicia faba L. (Vf) as the sole source of protein. Compared with pair-fed controls (PF), soleus muscles of Vf-fed rats showed increased (P < 0.05) synthesis and breakdown rates. In addition, the soleus of Vf-fed rats displayed a decrease (P < 0.05) in type I and an increase (P < 0.01) in type IIc fibers compared with that of PF animals. On the contrary, extensor digitorum longus muscles of both Vf-fed and PF rats showed an increase (P < 0.01) in type I and a reduction (P < 0.05) in type IIb fibers together with a decrease (P < 0.05) in the cross-sectional area of the latter fibers. Vf-fed rats exhibited a significant decrease in serum insulin (P < 0.05) and thyrotropin (P < 0.01) levels, together with an increase in plasma glucagon (P < 0.05) and 3,5,3'-triiodothyronine (P < 0.01) concentrations, compared with the PF group. Both Vf-fed and PF rats experienced an increase in corticosterone concentrations (P < 0.01 vs. control; P < 0.05 vs. PF). The muscle-specific changes in both protein metabolism and fiber type composition may partly depend on the hormonal changes that were observed after Vf intake.

Amino Acids↗

Pivotal role of nitric oxide in the control of blood pressure after leptin administration.

Leptin administration has been shown to increase renal, adrenal, and lumbar sympathetic nerve activity. However, this generalized sympathoexcitatory activity is not always followed by an increase in arterial pressure. The present study tested the hypothesis that leptin induces a release of nitric oxide (NO) that opposes the pressor effect of sympathoexcitation. The effect of intravenous administration of leptin (10, 100, and 1,000 microg/kg body wt) or vehicle on blood pressure (BP), heart rate (HR), and serum nitrite/nitrate concentrations of anesthetized Wistar rats was examined. At 90 min after injection, the three leptin doses tested increased serum NO concentrations 20.5, 33.1, and 89.5%, respectively (P < 0.001 vs. baseline). The effect of leptin on NO concentrations was significantly dose-dependent on linear trend testing (P = 0.0001). In contrast, leptin did not change serum nitrite/nitrate concentrations of fa/fa rats. Leptin administration to Wistar rats under NO synthesis inhibition (N(omega)-nitro-L-arginine methyl ester [L-NAME]) produced a statistically significant increase (P < 0.05) in both systolic BP and mean arterial pressure as well as in HR (P < 0.01). Injection of leptin into rats with pharmacologically induced ganglionic blockade (chlorisondamine) was followed by a decrease in BP and HR to values significantly lower (P < 0.01) than those observed with chlorisondamine treatment alone. The leptin-induced hypotension observed in the setting of ganglionic blockade was blocked by L-NAME. These findings raise the possibility that the leptin-induced release of NO may contribute to the homeostasis of BP.

Animals↗

Pre- and postprandial expression of the leptin receptor splice variants OB-Ra and OB-Rb in murine peripheral tissues.

Leptin receptors (OB-R) are widely distributed in peripheral tissues. However, the RT-PCR data published on the distribution of OB-R are not always consistent. The present study was undertaken in order to test whether the different muscle fiber type profile or the acute nutritional status in which tissue samples were excised from animals may influence OB-R expression. Six 12-week-old male Swiss-Webster mice were killed by decapitation either 1 h after feeding or after a 16-h fast, and the kidneys, testes, brown adipose tissue, gastrocnemius (G), soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected out. In parallel, muscle fibers obtained from other animals were classified on the basis of differences in the staining intensity for myofibrillar adenosinetriphosphatase. The expression of OB-R isoforms was assessed by RT-PCR and ethidium bromide staining. The signal for OB-Ra and OB-Rb was detected in all tissues examined. No differences were observed in samples obtained from either fed or fasted mice. G, SOL and EDL muscles showed the same pattern of OB-R expression. Neither the short-term nutritional changes of the animal as regards to the pre- versus the postprandial-state nor differences in muscle fiber type had any influence on the qualitative expression of the OB-R splice variants a and b in the murine tissues studied. However, quantitative differences cannot be ruled out.

Animals↗

Lipolytic effect of in vivo leptin administration on adipocytes of lean and ob/ob mice, but not db/db mice.

The present study has examined the effect of a single in vivo intraperitoneal injection of the adipocyte-derived hormone, leptin, on the in vitro lipolysis of fat cells of different types of mice. Administration of 1 and 10 mg leptin per kg body weight to ob/ob mice significantly increased (P < 0.0001) the basal lipolytic activity compared to ob/ob mice receiving vehicle solution (phosphate-buffered saline, PBS). The highest leptin dose tested (10 mg/kg body weight) produced a threefold increase in basal lipolysis. In lean mice administration of 10 mg leptin per kilogram of body weight produced an increase in basal lipolysis of 52.7% (P < 0.01). However, in db/db mice none of the three leptin doses injected had a significant effect on the lipolytic activity of adipocytes relative to basal lipolysis observed in db/db mice injected with PBS only. These data provide evidence for a lipolytic effect of leptin on white adipose tissue, which operates independently from changes in food intake, body weight, and the size of the fat stores.

Adipocytes↗

Age-related differences in the thermogenic and ponderal effects following the administration of fragment peptides from the rat ob protein.

The ob gene encodes a protein, which regulates satiety, metabolic rate and fat storage. The administration of a pool of five 20-amino-acid fragment peptides derived from the carboxy-terminal region of the ob protein produced a statistically significant reduction in body weight gain in adult rats, while rectal temperature showed a statistically significant increase. Administration of the same pool of peptides to young rats did not produce changes in body weight gain, although a statistically significant transient increase in rectal temperature was observed. These results envisage the possibility that small sequences of amino acids derived from the ob protein may mimic the effects of the whole protein on temperature and ponderal regulation. Furthermore, data suggest possible age-related differences in the response to leptin administration.

Aging↗

Leptin: physiology and pathophysiology.

The identification and sequencing of the ob gene and its product, leptin, in late 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. During this time, a considerable body of knowledge regarding leptin's actions has been accumulated and the field continues to expand rapidly. Currently there is particular interest in the interaction of leptin with other peripheral and neural mechanisms to regulate body weight, reproduction and immunological response. In this review, we attempt to place the current state of knowledge about leptin in the broader perspective of physiology, including its structural characteristics, receptors, binding proteins, signalling pathways, regulation of adipose tissue expression and production, secretion patterns, clearance mechanisms and functional effects. In addition, leptin's involvement in the pathophysiology of obesity, anorexia nervosa, diabetes mellitus, polycystic ovary syndrome, acquired immunodeficiency syndrome, cancer, nephropathy, thyroid disease, Cushing's syndrome and growth hormone deficiency will be reviewed.

Animals↗

In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin.

The present study has examined the effects of the adipocyte-derived hormone, leptin, on lipolysis in fat cells of different types of mice. Exposure to leptin (1.25.10(-6) M to 1.25.10(-12) M) increased (P < 0.01) the lipolytic activity of fat cells obtained from lean mice. A greater stimulation was observed when adipocytes from ob/ob mice were examined. Throughout the concentrations tested, the leptin-induced lipolysis observed in fat cells of lean animals was smaller than that obtained in ob/ob mice. The maximal lipolytic effect in obese animals was observed with 10(-8) M of OB protein. The lipolytic activity following the addition of 1.25.10(-10) M to 1.25.10(-6) M was significantly increased (P < 0.01) in ob/ob mice compared to lean animals. Adipocytes from ob/ob mice responded in a dose-dependent manner to the OB protein, while the leptin-induced lipolysis observed in lean animals was dose-independent. In contrast to lean and ob/ob mice, leptin did not stimulate lipolysis in adipocytes from db/db mice, which have a mutation in the leptin receptor gene. These in vitro studies suggest an autocrine/paracrine action of leptin on white fat cells and envisages the involvement of the OB protein, not only in centrally mediated pathways, but also in physiological functions which take place peripherally.

Adipocytes↗

Hormonal implications of the hypocholesterolemic effect of intake of field beans (Vicia faba L.) by young men with hypercholesterolemia.

This study examined the hypocholesterolemic effect and hormonal changes resulting from 30 d of supplementation with Vicia faba L. (field bean) flour of diets of young men (aged 18-21 y; n = 40) with borderline-high or high serum cholesterol values. All subjects (groups A-D) consumed the same basic diet. Additionally, volunteers in the control group (A) consumed 90 g control flour/d whereas those in the three bean groups received either 90 g cooked field bean flour (groups B and C) or 90 g raw field bean flour (group D) daily. Groups A and B included volunteers with borderline-high cholesterol values [5.2-6.2 mmol total cholesterol/L and 3.4-4.1 mmol low-density-lipoprotein (LDL) cholesterol/L]. Subjects in groups C and D had high serum cholesterol concentrations (total cholesterol > 6.2 mmol/L and LDL cholesterol > 4.1 mmol/L). After 30 d, serum glucose, insulin, triacylglycerol, total, LDL-cholesterol, and very-low-density-lipoprotein (VLDL)-cholesterol values were significantly lower than initial values in all subjects who consumed diets containing field bean flour (P < or = 0.0001, except for LDL-cholesterol concentrations in group C, for which P < or = 0.0007). Legume intake also resulted in a significant increase (P < or = 0.0001) in glucagon and high-density-lipoprotein cholesterol. Neither cortisol nor thyroid hormone values changed significantly. The results suggest that the hypocholesterolemic effect of field bean intake depends at least partly on a concomitant increase in glucagon and decrease in insulin values. The more marked reduction in triacylglycerol and VLDL-cholesterol concentrations in subjects who consumed raw field beans indicates a coparticipation of their thermolabile components.

Adolescent↗

Effect of aging on the rate of muscle protein turnover in rat.

The urinary excretion of Nt-methylhistidine (e-methylhistidine, 3-MH, an index related to myofibrillar protein breakdown), as well as the rate of L-[14C]-tyrosine incorporation into gastrocnemius muscle (ks, fractional rate of muscle protein synthesis, evaluated by the constant infusion method) have been measured to assess the effect of aging on the rate of skeletal muscle protein turnover. In addition, nucleic acids, muscle protein and serum corticosterone levels were determined. Weaning rats were fed a 10% lactalbumin diet and killed in groups of seven when they were 35, 60, 120 and 300 days old. Apart from the rate of growth, no major differences were found between 35- and 60-day old animals. However, as compared to the youngest rats, 120-day old rats showed a significant reduction in the relative weight of the four muscles excised. Plasma corticosterone levels, increased as the animals became older. Finally, in the 300-day old rats, the reduced rate of growth was accompanied by a significant reduction in the relative organ weight (with the exception of soleus), 3-MH and Ks. It is concluded that aging caused a reduction in the rates of both protein breakdown and synthesis. The reduced muscle breakdown may not be due to a relative reduced muscle mass in elder rats since urinary 3-MH remained low even when expressed per creatinine output.

Aging↗

Regulation of energy balance and adiposity: a model with new approaches.

Obesity etiology and treatment have been fraught with disappointment for researchers, because the mechanisms regulating fuel homeostasis and adiposity are incompletely understood. It can now be hypothesized in the light of new evidences that the control of body weight and composition depends upon an axis with three interrelated and self-controlled components: 1) food intake; 2) nutrient turnover and thermogenesis and 3) body fat stores, all of which underly complex feedback mechanisms. This approach considers two of the most relevant recent findings in the field (leptin and beta 3-adrenoceptors), adding new views to previous metabolic models of obesity. This perspective supplies some additional clues to the understanding of body composition regulation as well as the potential involvement of genetic and hypothalamic disorders in the onset of obesity.

Adipose Tissue↗