Maresin1 is a predictive marker of new digital ulcers in systemic sclerosis patients.

BACKGROUND: Digital ulcers (DUs) are one of the main causes of disability among systemic sclerosis (SSc) patients. The inflammation plays a crucial role in mediating the pathophysiological process underlying SSc. Objective of this study was to evaluate Maresin1 (MaR1) serum levels in SSc patients and in healthy controls (HC). Secondary aims were to evaluate the relationship between MaR and diseases variables and to assess the predictive role of MaR1 in the development of new digital ulcers (DUs) during 18 weeks follow-up. METHODS: MaR1 serum level was evaluated in 55 SSc patients and 24 HC. In SSc patients, clinical assessment was performed at baseline and after 18 week follow-up by the same-blinded observer on serum MaR1 levels. RESULTS: MaR1 was significantly lower in SSc patients than in HC [367 pg/ml (IQR 304-468.3 pg/ml) vs 467.7 pg/ml (IQR 422-522 pg/ml), p < 0.001]. During follow-up, six patients (10.9%) developed DUs. MaR1 was higher in SSc patients with new DUs than in patients without new DUs [518.2 pg/ml (IQR 468.2-596.5 pg/ml) vs 355 pg/ml (IQR 299.8-444.7 pg/ml), p < 0.01]. Free survival from new DUs is significantly lower in SSc patients with increased MaR1 serum level than in SSc patient with normal MaR1 serum level. In multivariate analysis, serum level of MaR1 > 393.2 pg/ml is a predictive marker for new DUs. CONCLUSION: In SSc patients, MaR1 is reduced compared to HC and it is a predictive marker of new DUs.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer.

BACKGROUND: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia. METHODS: We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5. RESULTS: We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027). CONCLUSION: In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.

Timing of antioxidant supplementation is critical in improving anorexia in an experimental model of cancer.

Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1ß levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.

Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement.

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular-pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208-19,941) vs 8556 pg/ml (6820-11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = - 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = - 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular-pulmonary arterial coupling.

Changes of gene expression in peripheral blood mononuclear cells of lung cancer patients with or without anorexia.

BACKGROUND & AIMS: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia. METHODS: Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes. RESULTS: RNA-Seq analysis revealed among groups a large number of differentially expressed genes mainly implicated in immune system regulation, oxidative stress and cytokine-mediated inflammation signaling pathways. In particular, we identified a total of 983 DEGs (843 up-regulated; 140 down-regulated) in anorexic cancer compared to controls. A selected number of DEGs including ADAM8, SMAD4, CCR4 and CLU were differentially expressed within cancer group according to the presence/absence of anorexia. In terms of RT-qPCR, ADAM8 was less expressed in cancer patients than controls (p < 0.001), and in anorexic patients vs controls (p = 0.001). The expression of SMAD4 was lower in cancer vs controls (p = 0.005), and in anorexic patients vs controls (p = 0.009). We observed lower CCR4 expression in both anorexic and non-anorexic vs control (p = 0.004, p = 0.011, respectively) and a similar trend was present for CLU. CONCLUSIONS: Our data shed new light on the role of specific genes and their associated molecular pathways as potential key mechanisms for the development of anorexia and may represent a novel landmark for understanding the complex pathophysiology of impaired appetite in cancer.

Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats.

Increased cytokine expression contributes to the pathogenesis of cancer anorexia?cachexia syndrome. Carnitine may reduce inflammation in chronic diseases. We tested the effects of L-propionylcarnitine (PC group) or saline (C group) on food intake (FI), body composition, and inflammatory status of MCA-sarcoma-bearing rats. On tumor appearance, rats were randomly assigned to daily i.p. injection of L-propionylcarnitine (250 mg/kgBW/d; n = 8) or saline (equal volume; n = 8). FI and fat-free mass wasting improved in PC rats only (p < .01 vs. controls). Cytokines? levels decreased in PC rats vs. controls (p < .02). Results suggest that carnitine may ameliorate cancer anorexia?cachexia, via reduction of the inflammatory status.

Stimulation of the nicotine antiinflammatory pathway improves food intake and body composition in tumor-bearing rats.

Inflammation contributes to the pathogenesis of cancer anorexia-cachexia syndrome. Nicotine administration reduces cytokine levels and mortality during sepsis. Therefore, nicotine administration may result in improved anorexia-cachexia. Sixteen male Fischer rats inoculated with MCA sarcoma were assigned to random injections of nicotine (NIC; 200 mg/kg BW/d) or saline (C). Food intake (FI), body weight, body composition, interleukin (IL)-1, IL-6 levels were evaluated. Data were analyzed via Student's t-test for paired and unpaired data and ANOVA. FI started declining 12 days after tumor inoculation both in C and NIC rats, but the decline was significantly attenuated by nicotine administration. At the end of the study, lean body mass wasting was more severe in C rats than in NIC rats (P<0.05), whereas a trend toward attenuation of fat mass depletion was observed. IL-1 circulating levels were significantly lower in NIC rats than in C rats (114±21 pg/mL vs. 190±35 pg/mL, respectively; P<0.01), whereas the reduction of IL-6 levels in NIC rats was only marginally not significant when compared to C rats (555±174 pg/mL vs. 721±160 pg/mL, respectively; P=0.06). Our data suggest that the nicotinic antiinflammatory pathway may represent an interesting and possibly effective therapy for anorexia-cachexia syndrome.

Plasma enterobacterial ClpB levels and ClpB- and α-MSH-reactive immunoglobulins in lung cancer patients with and without anorexia.

OBJECTIVES: Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated. METHODS: To address this question, we analyzed plasma ClpB concentrations as well as levels and affinities of anti-ClpB and α-MSH-reactive antibodies in patients with lung cancer with and without anorexia as compared with body mass index-matched healthy controls with normal appetite. RESULTS: We found that plasma ClpB concentrations were significantly lower in non-anorexic patients with cancer than those of the control group (P = 0.028). In contrast, patients with cancer and anorexia had lower levels of anti-ClpB immunoglobulins (Ig)M (P < 0.0001) and of both α-MSH IgM and IgG (P < 0.05) with respect to controls. Moreover, in patients with cancer and anorexia, anti-ClpB IgG showed a trend of lower affinities compared with non-anorexic patients (P = 0.05). CONCLUSIONS: Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.

Association Between Metabolic and Hormonal Derangements and Professional Exposure to Urban Pollution in a High Intensity Traffic Area.

Rationale: Studies suggest a relation between exposure to air particulate matter (PM)2.5 pollution and greater cardiovascular morbidity, as well as increased risk for obesity and diabetes. We aimed to identify association(s) between nutritional and metabolic status and exposure to environmental pollution in a cohort of policemen exposed to high levels of air pollution. Methods: We considered adult municipal policemen, working in an urban area at high-traffic density with documented high levels of air PM2.5 (exposed group) compared to non-exposed policemen. Clinical characteristics, including the presence/absence of metabolic syndrome, were recorded, and serum biomarkers, including adiponectin, leptin, and ghrelin, were assessed. Results: One hundred ninety-nine participants were enrolled, 100 in the exposed group and 99 in the non-exposed group. Metabolic syndrome was documented in 32% of exposed group and in 52.5% of non-exposed group (P = 0.008). In the exposed group, we found a positive correlation between body mass index and serum leptin as well as in the non-exposed group (P < 0.0001). Within the exposed group, subjects with metabolic syndrome showed lower serum adiponectin (P < 0.0001) and higher leptin (P = 0.002) levels with respect to those without metabolic syndrome, whereas in the non-exposed group, subjects with metabolic syndrome showed only higher leptin levels when compared to those without metabolic syndrome (P = 0.01). Among the participants with metabolic syndrome, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones (P = 0.007). When comparing the exposed and non-exposed groups, after stratifying participants for Homeostatic Model Assessment for Insulin Resistance >2.5, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones (P = 0.038). Conclusions: Exposure to air PM pollution was associated with lower levels of adiponectin in adult males with metabolic syndrome.

Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients.

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. METHODS: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). RESULTS: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1ß, and tumor necrosis factor-α concentrations in either group. CONCLUSIONS: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.

DHA Oral Supplementation Modulates Serum Epoxydocosapentaenoic Acid (EDP) Levels in Breast Cancer Patients.

INTRODUCTION: The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations. METHODS: BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry. RESULTS: 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients (P < 0.00001) and in controls (P < 0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation (P = 0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A (P = 0.02). CONCLUSIONS: DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.

Effect of Oral Docosahexaenoic Acid (DHA) Supplementation on DHA Levels and Omega-3 Index in Red Blood Cell Membranes of Breast Cancer Patients.

Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition. Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P-value < 0.05 was considered statistically significant. Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group), 12 patients with familiar positive history for BC (F group), 10 patients with sporadic BC (S group), and 10 healthy controls (C group). DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls (P < 0.001). No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (ß = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as "good seafood consumers" showed at baseline DHA and omega-3 index higher with respect to "low seafood consumers" (P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in "low seafood consumers" with respect to "good seafood consumers" (P < 0.0001). Conclusion: DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy controls, seem to be associated with greater ability of DHA incorporation. Larger samples of BC patients are necessary to confirm our observation.

Autophagy is induced in the skeletal muscle of cachectic cancer patients.

Basal rates of autophagy can be markedly accelerated by environmental stresses. Recently, autophagy has been involved in cancer-induced muscle wasting. Aim of this study has been to evaluate if autophagy is induced in the skeletal muscle of cancer patients. The expression (mRNA and protein) of autophagic markers has been evaluated in intraoperative muscle biopsies. Beclin-1 protein levels were increased in cachectic cancer patients, suggesting autophagy induction. LC3B-I protein levels were not significantly modified. LC3B-II protein levels were significantly increased in cachectic cancer patients suggesting either increased autophagosome formation or reduced autophagosome turnover. Conversely, p62 protein levels were increased in cachectic and non-cachectic cancer patients, suggesting impaired autophagosome clearance. As for mitophagy, both Bnip3 and Nix/Bnip3L show a trend to increase in cachectic patients. In the same patients, Parkin levels significantly increased, while PINK1 was unchanged. At gene level, Beclin-1, p-62, BNIP3, NIX/BNIP3L and TFEB mRNAs were not significantly modulated, while LC3B and PINK1 mRNA levels were increased and decreased, respectively, in cachectic cancer patients. Autophagy is induced in the skeletal muscle of cachectic cancer patients, although autophagosome clearance appears to be impaired. Further studies should evaluate whether modulation of autophagy could represent a relevant therapeutic strategy in cancer cachexia.

Caloric restriction and L-carnitine administration improves insulin sensitivity in patients with impaired glucose metabolism.

BACKGROUND: Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L-carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM-2) is still controversial. The aim of the study was to explore the role of L-carnitine supplementation in influencing insulin sensitivity. METHODS: A randomized controlled study involving adult outpatients was designed. Adult patients referred to the outpatient clinic and within 10 days of the diagnosis of IFG or DM-2 were consecutively enrolled. Exclusion criteria were concomitant antidiabetic therapy and modifications of lifestyle during the previous 4 weeks. Patients were randomly assigned to receive a hypocaloric diet for 10 days (group C; n = 8) or the same dietetic regimen in addition to oral L-carnitine (2 g twice daily) supplementation (group LC; n = 8). Oral glucose tolerance test (OGTT), fasting plasma insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at the beginning and end of the study. Data were statistically analyzed using the Student t test for paired and unpaired data. RESULTS: OGTT at 2 hours improved in both groups. Only in the L-carnitine-supplemented group did plasma insulin levels and HOMA-IR significantly decrease when compared to baseline values. CONCLUSIONS: Considering the role of caloric restriction in increasing the intestinal uptake of carnitine, the results suggest that oral L-carnitine administration, when associated with a hypocaloric feeding regimen, improves insulin resistance and may represent an adjunctive treatment for IFG and DM-2.