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C Grunfeld

Publications and source records attributed to C Grunfeld.

At least 55 records · Page 3Linked to original sources
PubMed1998

IL-1 beta mediates leptin induction during inflammation.

Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue and plays an important role in the control of food intake. Administration of lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA and protein levels. To investigate the role of IL-1 beta and IL-6 in leptin expression during inflammation, we used IL-1 beta-deficient (-/-) and IL-6 -/- mice. Mice were injected intraperitoneally with LPS or subcutaneously with turpentine, as models of systemic or local inflammation, respectively. In IL-1 beta +/+ mice, both LPS and turpentine increased leptin mRNA and circulating leptin. In contrast, neither LPS nor turpentine increased leptin levels in IL-1 beta -/- mice. In IL-6 +/+ or IL-6 -/- mice, turpentine increased leptin protein to comparable levels. We conclude that IL-1 beta is essential for leptin induction by both LPS and turpentine in mice, but IL-6 is not.

Animals↗
PubMed1998

Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin.

Alterations in triglyceride and cholesterol metabolism often accompany inflammatory diseases and infections. We studied the effects of endotoxin (lipopolysaccharide [LPS]) and cytokines on hepatic sphingolipid synthesis, activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid synthesis, and lipoprotein sphingolipid content in Syrian hamsters. Administration of LPS induced a 2-fold increase in hepatic SPT activity. The increase in activity first occurred at 16 hours, peaked at 24 hours, and was sustained for at least 48 hours. Low doses of LPS produced maximal increases in SPT activity, with half-maximal effect seen at approximately 0.3 microg LPS/100 g body weight. LPS increased hepatic SPT mRNA levels 2-fold, suggesting that the increase in SPT activity was due to an increase in SPT mRNA. LPS treatment also produced 75% and 2.5-fold increases in hepatic sphingomyelin and ceramide synthesis, respectively. Many of the metabolic effects of LPS are mediated by cytokines. Interleukin 1 (IL-1), but not tumor necrosis factor, increased both SPT activity and mRNA levels in the liver of intact animals, whereas both IL-1 and tumor necrosis factor increased SPT mRNA levels in HepG2 cells. IL- produced a 3-fold increase in SPT mRNA in HepG2 cells, and the half-maximal dose was 2 ng/mL. IL-1 also increased the secretion of sphingolipids into the medium. Analysis of serum lipoprotein fractions demonstrated that very low density lipoprotein, intermediate density lipoprotein, and low density lipoprotein isolated from animals treated with LPS contained significantly higher amounts of ceramide, glucosylceramide, and sphingomyelin. Taken together, these results indicate that LPS and cytokines stimulate hepatic sphingolipid synthesis, which results in an altered structure of circulating lipoproteins and may promote atherogenesis.

Acyltransferases↗
PubMed1998

Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis.

After permeability barrier perturbation there is an increase in the mRNA levels for key enzymes necessary for lipid synthesis in the epidermis. The mechanism(s) responsible for this regulation is unknown. Sterol regulatory element binding proteins-1a, 1c, and -2 (SREBPs) control the transcription of enzymes required for cholesterol and fatty acid t synthesis in response to modulations of sterol levels. We now demonstrate that SREBP-2 is the predominant SREBP in human keratinocytes and murine epidermis, while SREBP-1 is not detected. Sterols regulate SREBP-2 mRNA levels in keratinocytes and the epidermis and the proteolytic cleavage of SREBP-2 to the mature active form in keratinocytes. In parallel to the increase in mature active SREBP, there is a coordinate increase in mRNA levels for cholesterol (HMG-CoA reductase, HMG-CoA synthase, farnesyl diphosphate synthase, and squalene synthase) and fatty acid (acetyl-CoA carboxylase, fatty acid synthase) synthetic enzymes. However, mRNA levels for serine palmitoyl transferase (SPT), the first committed step for ceramide synthesis, do not increase in parallel. The increase of mRNA for enzymes required for epidermal cholesterol and fatty acid synthesis is consistent with both the previously described early increase of cholesterol and fatty acid synthesis after barrier disruption and a role for SREBP-2 in the regulation of cholesterol and fatty acid synthesis for epidermal barrier homeostasis. In contrast, SPT appears to be regulated by different mechanisms, consistent with the different time course of its stimulation after barrier disruption.

Acetyl-CoA Carboxylase↗
PubMed1998

Beneficial effects of cytokine induced hyperlipidemia.

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.

Acute-Phase Proteins↗
PubMed1998

Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines.

We studied the effect of endotoxin (LPS), and cytokines (TNF, IL-1, and IL-6) on hepatic microsomal triglyceride transfer protein (MTP) mRNA levels in vivo in Syrian hamsters and in vitro in HepG2 cells. LPS, interleukin-1 (IL-1), and to a lesser extent tumor necrosis factor (TNF) significantly decreased MTP mRNA levels in hamster liver. These effects required several hours. Furthermore, IL-1 and IL-6 significantly decreased MTP mRNA levels in HepG2 cells. This decrease appeared soon after IL-1 administration (8 h) and at very low doses (0.1 ng/ml). MTP activity and protein levels of the large subunit of MTP also decreased modestly in HepG2 cells with prolonged cytokine treatment. IL-1 reduced the expression of an MTP promoter luciferase construct to a similar degree as seen with MTP mRNA, indicating that transcriptional regulation plays a major role in the decrease of MTP gene expression. Deletional analysis of the MTP promoter identified the region -121 to -88 bp upstream to the coding sequence as the site of the negative regulation by IL-1. This region contains an insulin response element (IRE), activating protein 1 (AP-1), hepatic nuclear factor 1 (HNF-1) and hepatic nuclear factor 4 (HNF-4) consensus sequences; mutations of the IRE and HNF-4 sites did not affect the response to IL-1. In contrast, mutating AP-1 or HNF-1 sites led to a marked decrease in basal expression and the loss of the IL-1 effect, suggesting that an intact AP-1 and/or HNF-1 regulatory element are crucial for the IL-1 regulation of MTP gene expression. However, prolonged incubation with IL-1 did not alter HepG2 apolipoprotein B secretion suggesting that MTP mRNA down-regulation does not contribute significantly to the cytokine-induced effects on lipid metabolism.

Animals↗
PubMed1997

Amphiregulin and nerve growth factor expression are regulated by barrier status in murine epidermis.

Disruption of the murine permeability barrier by solvents or tape stripping stimulates a homeostatic repair response that includes increased epidermal DNA synthesis. To identify potential mediators of the increase in DNA synthesis, we have measured epidermal levels of mRNAs encoding various growth factors after acute barrier disruption. In this study, mRNAs for amphiregulin and nerve growth factor were each shown to increase over controls at 30 min, reach peak levels of 12- to 30-fold at 1-2 h, and return to control levels by 6 h after tape stripping. A similar time course for the increase of amphiregulin and nerve growth factor mRNAs was observed after an unrelated form of barrier disruption, i.e., acetone treatment. Furthermore, artificial restoration of the barrier by Latex occlusion, immediately following barrier disruption by acetone treatment, inhibited the increase in epidermal amphiregulin and nerve growth factor mRNA levels, indicating that barrier status regulates the production of these growth factors. In contrast, mRNA levels of transforming growth factor-beta1, an inhibitory growth factor, were unchanged at early times and decreased by 53% (p < 0.02) 6 h after tape stripping, whereas mRNA levels of transforming growth factor-alpha remained unchanged at all times after acute barrier disruption. These results suggest that barrier disruption stimulates the expression of amphiregulin and nerve growth factor. Together, these regulators of keratinocyte growth and differentiation may be responsible for the increased proliferative response that is associated with barrier disruption.

Amphiregulin↗
PubMed1997

Permeability barrier disruption coordinately regulates mRNA levels for key enzymes of cholesterol, fatty acid, and ceramide synthesis in the epidermis.

The extracellular lipids of the stratum corneum, which are comprised mainly of cholesterol, fatty acids, and ceramides, are essential for epidermal permeability barrier function. Moreover, disruption of the permeability barrier results in an increased cholesterol, fatty acid, and ceramide synthesis in the underlying epidermis. This increase in lipid synthesis has been shown previously to be due to increased activities of HMG-CoA reductase, acetyl-CoA carboxylase, fatty acid synthase and serine palmitoyl transferase, key enzymes of cholesterol, fatty acid, and ceramide synthesis, respectively. In the present study, we determined whether the mRNA levels for the key enzymes required for synthesis of these three classes of lipids increase coordinately during barrier recovery. By northern blotting, the steady-state mRNA levels for HMG-CoA reductase, HMG-CoA synthase, farnesyl pyrophosphate synthase, and squalene synthase, key enzymes for cholesterol synthesis, all increased significantly after barrier disruption by either acetone or tape stripping. Additionally, the steady-state mRNA levels of acetyl-CoA carboxylase and fatty acid synthase, required for fatty acid synthesis, as well as serine palmitoyl transferase, the rate-limiting enzyme of de novo ceramide synthesis, also increased. Furthermore, artificial restoration of the permeability barrier by occlusion after barrier disruption prevented the increase in mRNA levels for all of these enzymes, except farnesyl pyrophosphate synthase, indicating a specific link of the increase in mRNA levels to barrier requirements. The parallel increase in epidermal mRNA levels for the enzymes required for cholesterol, fatty acid, and ceramide synthesis may be due to one or more transcription factors that regulate lipid requirements for permeability barrier function in keratinocytes.

Acyltransferases↗
PubMed1997

Barrier disruption increases gene expression of cytokines and the 55 kD TNF receptor in murine skin.

The signalling mechanisms that regulate epidermal permeability barrier homeostasis are not known. Previous Northern blot analysis showed that both acute and chronic barrier disruption increase mRNA levels of several cytokines in murine epidermis. To further characterize the epidermal response to barrier abrogation, we used more sensitive, multi-probe RNase protection assays to measure the mRNA levels of additional cytokines, as well as cytokine receptors in acute and chronic models of barrier disruption. Normal mouse epidermis expressed interleukin (IL)-1 alpha, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-6 mRNAs. Following tape-stripping, only the mRNA levels for TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 increased at 2.5 and 7 h, and returned toward normal levels by 18 h. No mRNAs encoding TNF-beta, IL-2, IL-3, IL-4 or IL-5, were detected in the epidermis either under basal conditions or after tape-stripping. Similarly, in a chronic model, essential fatty acid deficiency, epidermal levels of TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 mRNAs, but not IFN-gamma mRNA, were elevated over controls; and again, mRNAs for the remaining probed cytokines were not detected. In contrast, in the dermis, only IL-1 beta mRNA levels increased 2.5 h after tape-stripping, and remained elevated at 18 h. mRNAs encoding the IL-1 (p60), IFN-gamma and IL-6 receptors were present in epidermis, but their levels remained unchanged following either acute or chronic barrier disruption. In contrast, epidermal TNF (p55) receptor mRNA levels were increased by 87% (P < 0.01) at 2.5 h, returned to control levels at 7 h and were increased by 68% (P < 0.03) at 18 h after tape-stripping. The increase at 2 h was confirmed by Northern blot analysis and was not prevented by latex occlusion performed immediately after tape-stripping mRNAs for the IL-1 (p80) receptor and TNF (p75) receptor were not detected in epidermis. Low levels of TNF (p55) receptor mRNA were present in the dermis, and they remained unchanged after tape-stripping. The presence of specific receptor mRNAs in the epidermis and dermis suggests that these tissues are capable of responding in an autocrine and/or paracrine fashion to the cognate cytokines. These results suggest that epidermal cytokines produced after barrier disruption may initiate a cytokine cascade which could regulate cytokine and cytokine receptor production and/or inflammatory responses.

Animals↗
PubMed1997

LPS-induced anorexia in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice.

Administration of endotoxin (lipopolysaccharide, LPS) induces profound anorexia. Injection of leptin decreases food intake in mice. Recently, we reported that LPS and cytokines increase leptin levels in hamsters. To further investigate the role of leptin in the LPS-induced anorexia, we administered LPS to leptin receptor-deficient (db/db) and leptin-deficient (ob/ob) mice. We found that LPS caused anorexia in both db/db and ob/ob mice. As might be predicted if leptin had a role in anorexia, the db/db mice were somewhat resistant to LPS-induced anorexia. However the ob/ob mice were more sensitive to LPS-induced anorexia. No differences between db/db and ob/ob mice and their respective littermate were observed in circulating tumor necrosis factor levels after LPS. These data suggest that leptin per se is not essential for LPS-induced anorexia.

Analysis of Variance↗
PubMed1997

Parathyroid hormone-related protein is induced in the adult liver during endotoxemia and stimulates the hepatic acute phase response.

Previously, we reported that PTH-related protein (PTHrP) gene expression is induced in vital organs, including the liver, during endotoxemia. The liver plays a central role in the acute phase response (APR), a cytokine-mediated host defense against infection and inflammation that includes increased production of acute phase proteins and lipids by hepatocytes. Because PTHrP is thought to act locally at its site of production, in vivo studies were carried out to determine whether PTHrP could contribute to the induction of the hepatic APR. Hepatic PTHrP messenger RNA (mRNA) levels were induced acutely in rat liver in response to a near lethal dose of endotoxin. PTHrP protein, which was located by immunohistochemical staining in hepatocytes from both control and LPS-treated rats, was markedly induced in periportal hepatocytes in response to LPS treatment. Co-incident with this transient increase in PTHrP gene expression, PTH/PTHrP receptor mRNA levels were down-regulated. Administration of PTHrP(1-34), a PTH/PTHrP receptor agonist, to mice increased hepatic serum amyloid A (SAA) mRNA levels as well as circulating levels of SAA. In addition, PTHrP(1-34) increased serum triglyceride (TG) levels in rats and mice in a dose-dependent fashion. The hypertriglyceridemic effect of PTHrP(1-34) was accompanied by an increase in hepatic fatty acid synthesis. In contrast, PTHrP(7-34) amide, a receptor antagonist, had no effect on serum SAA or TG levels. These results, which provide evidence for the regulated expression of PTHrP in adult liver, suggest that PTHrP may be one additional member of the cytokine cascade produced locally in liver that can act to stimulate the hepatic acute phase response.

Acute-Phase Reaction↗
PubMed1997

Abnormalities of apolipoprotein E in the acquired immunodeficiency syndrome.

Given the important role of apolipoprotein E (apoE) in triglyceride metabolism, we analyzed plasma levels and degree of sialylation of apoE in subjects with the acquired immunodeficiency syndrome (AIDS), a disorder accompanied by hypertriglyceridemia. Levels of apoE were significantly increased (1.84-fold) and correlated with plasma triglycerides (r = .663, P < .001) in AIDS. Subjects with AIDS and the apoE3/E2 phenotype showed the most prominent increases in both plasma triglyceride and apoE levels (3.4 and 2.2-fold over controls). Additionally, apoE from subjects with AIDS showed an increased amount of sialylation, compared with controls (34% increase in apoE3/E3 subjects). Increased sialylation correlated with the increase in apoE levels. In contrast, there was no increase in sialylation of apo C-III in AIDS. Thus, triglyceride levels in AIDS are influenced by apoE subtype and subjects with AIDS show changes in apoE structure.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Endotoxin, tumor necrosis factor, and interleukin-1 decrease hepatic squalene synthase activity, protein, and mRNA levels in Syrian hamsters.

Recent studies have shown that endotoxin (LPS) administration to Syrian hamsters markedly increased hepatic HMG-CoA reductase activity, protein mass, and mRNA levels, but only produced a modest increase in hepatic cholesterol synthesis, suggesting that LPS may also influence other key enzymes involved in the regulation of cholesterol metabolism. In the present study, we have examined the effect of LPS and cytokines on the activity, protein mass, and mRNA level of squalene synthase, which is the first committed enzyme in cholesterol biosynthesis and is located at a branch point in the mevalonate pathway. Our results demonstrate that LPS administration produces a marked decrease in the mRNA levels of squalene synthase. This decrease in squalene synthase mRNA occurred very rapidly (90 min after LPS) and required relatively small doses of LPS (1 microg/100 gm body weight). LPS also significantly decreased squalene synthase activity and protein mass. Finally, LPS produced a marked decrease in squalene synthase mRNA, activity, and protein levels when the basal levels of squalene synthase expression were increased 4-fold by prior treatment with bile acid binding resin, colestipol. Tumor necrosis factor and interleukin-1, which mediate many of the metabolic effects of LPS, also decreased hepatic squalene synthase activity and mRNA levels. Taken together, our results suggest that the discordant regulation of HMG-CoA reductase and squalene synthase during the host response to infection and inflammation may have substantial effects on the regulation of substrate flux into the non-sterol pathways of mevalonate metabolism.

Animals↗
PubMed1996

Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group.

BACKGROUND: Body wasting, particularly loss of body cell mass, is an increasingly prevalent acquired immunodeficiency syndrome (AIDS)-defining condition and is an independent risk factor for death in patients infected with the human immunodeficiency virus (HIV). Treatment with growth hormone for 7 days resulted in weight gain and nitrogen retention, but the long-term effects of this treatment in patients with HIV-associated wasting are not known. OBJECTIVE: To evaluate the long-term effect of treatment with growth hormone on weight, body composition, functional performance, and quality of life in patients with HIV-associated wasting. DESIGN: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING: Outpatient university and community-based patient care facilities. PATIENTS: 178 HIV-infected patients with documented unintentional weight loss of at least 10% or weight less than 90% of the lower limit of ideal body weight. INTERVENTION: Patients were randomly assigned to receive either recombinant human growth hormone, 0.1 mg/kg of body weight per day (average dosage, 6 mg/d) (n = 90) or placebo (n = 88) for 12 weeks. MEASUREMENTS: Weight; body fat, lean body mass, and bone mineral content (measured by dual-energy x-ray absorptiometry); total body water (by deuterium oxide dilution); extracellular water (by sodium bromide dilution); work output (by treadmill exercise); quality of life; and safety of treatment. RESULTS: Treatment with growth hormone resulted in a sustained and statistically significant increase in weight (mean increase +/- SD, 1.6 +/- 3.7 kg [P < 0.001]) and lean body mass (3.0 +/- 3.0 kg [P < 0.001]), accompanied by a decrease in body fat (-1.7 +/- 1.7 kg [P < 0.001]). In contrast, in patients receiving placebo, weight (increase, 0.1 +/- 3.1 kg), lean body mass (decrease, 0.1 +/- 2.0 kg), and body fat (decrease, 0.3 +/- 2.2 kg) did not change significantly from baseline. Differences between groups at week 12 were statistically significant (P = 0.011 for body weight and P < 0.001 for lean body mass and body fat). A greater increase in treadmill work output was noted in the group receiving growth hormone (increase, 99 +/- 293 kg. m/min) compared with the group receiving placebo (increase, 20 +/- 233 kg.m/min)(P = 0.039). Health status (quality of life) scores did not differ between groups at baseline or after treatment. Days of disability and use of medical resources were the same for both groups. Treatment was was well tolerated; no significant differences were seen between groups in clinical events, progression of AIDS, CD4+ or CD8+ cell counts, or viral burden. CONCLUSION: Treatment with growth hormone increases body weight, lean body mass, and treadmill work output and appears to be a safe and potentially effective therapy in patients with HIV-associated wasting.

Adult↗
PubMed1996

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters.

The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin decreases food intake. Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection. Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters. In fasted adipose tissue to levels similar to fed control animals. There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake. TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin in mRNA in adipose tissue. As assessed by immuknoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA. Induction of leptin during the host response to infection may contribute to the anorexia of infection.

Adipocytes↗
PubMed1996

Growth hormone replacement in healthy older men improves body composition but not functional ability.

OBJECTIVE: To determine whether growth hormone replacement in older men improves functional ability. DESIGN: Randomized, controlled, double-blind trial. SETTING: General community. PATIENTS: 52 healthy men older than 69 years of age with well-preserved functional ability but low baseline insulin-like growth factor 1 levels. INTERVENTION: Growth hormone (0.03 mg/kg of body weight) or placebo given three times a week for 6 months. MEASUREMENTS: Body composition, knee and hand grip muscle strength, systemic endurance, and cognitive function. RESULTS: The participants' mean age was 75.0 years (range, 70 to 85 years). At 6 months, lean mass had increased on average by 4.3% in the growth hormone group and had decreased by 0.1% in the placebo group, a difference of 4.4 percentage points (95% CI, 2.1 to 6.8 percentage points). Fat mass decreased by an average of 13.1% in the growth hormone group and by 0.3% in the placebo group, a difference of 12.8 percentage points (CI, 8.6 to 17.0 percentage points). No statistically or clinically significant differences were seen between the groups in knee or hand grip strength or in systemic endurance. The mean Trails B score in the growth hormone group improved by 8.5 seconds, whereas scores in the placebo group deteriorated by 5.0 seconds, a difference of 13.5 seconds (CI, 3.1 seconds to 23.9 seconds; P = 0.01). However, the growth hormone group's score on the Mini-Mental Status Examination deteriorated by 0.4, whereas the placebo group's score improved by 0.2, a difference of 0.6 (P = 0.11). The two treatment groups had almost identical scores on the Digit Symbol Substitution Test (P > 0.2). Twenty-six men in the growth hormone group had 48 incidents of side effects, and 26 placebo recipients had 14 incidents of side effects (P = 0.002). Dose reduction was required in 26% of the growth hormone recipients and in none of the placebo recipients (P < 0.001). CONCLUSIONS: Physiologic doses of growth hormone given for 6 months to healthy older men with well-preserved functional abilities increased lean tissue mass and decreased fat mass. Although body composition improved with growth hormone use, functional ability did not improve. Side effects occurred frequently.

Affect↗
PubMed1996

Beta-nerve growth factor as a mediator of the acute phase response in vivo.

Nerve growth factor (NGF) is increased during inflammation and stress. Stress-induced increases in specific serum proteins, such as serum amyloid A (SAA) and serum triglyceride (TG) levels, are part of the acute phase response which is mediated by cytokines. We now report the effect of systemic administration of beta-NGF on levels of serum lipids and SAA. Beta-NGF induced a rapid and sustained increase in serum TG and free fatty acid (FFA) in a dose dependent manner, while decreasing serum cholesterol levels in rats. Additionally, beta-NGF increased hepatic mRNA levels and serum concentrations of SAA at 16 hours in mice. Thus, beta-NGF joins the list of cytokines and growth factors that can mediate the acute phase response.

Animals↗
PubMed1996

Regulation of lipid metabolism by cytokines during host defense.

Lipid metabolism is extensively regulated during the host response to infection. As with other aspects of the host response, these events are mediated by cytokines, including tumor necrosis factor, interleukin 1 (IL-1), IL-6, and the interferons. Cytokines can decrease lipoprotein lipase and increase lipolysis in cultured fat cells. In vivo, many cytokines increase serum triglycerides by increasing very-low-density lipoprotein production. Interferons increase triglycerides predominantly by decreasing lipoprotein lipase activity and triglyceride clearance. These changes in lipid metabolism do not cause cachexia. Rather, they represent part of the host defense, as lipoproteins scavenge infectious particles such as endotoxin.

Adipocytes↗