Cardiolipin content is involved in liver mitochondrial energy wasting associated with cancer-induced cachexia without the involvement of adenine nucleotide translocase.

Cancer-induced cachexia describes the progressive skeletal muscle wasting associated with many cancers leading to shortened survival time in cancer patients. We previously reported that cardiolipin content and energy-wasting processes were both increased in liver mitochondria in a rat model of peritoneal carcinosis (PC)-induced cachexia. To increase the understanding of the cellular biology of cancer cachexia, we investigated the involvement of adenine nucleotide translocator (ANT) in mitochondrial energy-wasting processes in liver mitochondria of PC and pair-fed control rats and its interactions with cardiolipin in isolated liver mitochondria from healthy rats exposed to cardiolipin-enriched liposomes. We showed in this study that functional ANT content was decreased in liver mitochondria from PC rats but without any effects on the efficiency of ATP synthesis. Moreover, non-phosphorylating energy wasting was not affected by saturating concentrations of carboxyatractylate (CAT), a potent inhibitor of ANT, in liver mitochondria from PC rats. Decreased efficiency of ATP synthesis was found in normal liver mitochondria exposed to cardiolipin-enriched liposomes, with increased non-phosphorylating energy wasting, thus mimicking mitochondria from PC rats. However, the functional ANT content in these cardiolipin-enriched mitochondria was unchanged, although non-phosphorylating energy wasting was reduced by CAT-induced inhibition of ANT. Finally, non-phosphorylating energy wasting was increased in cardiolipin-enriched mitochondria with substrates for complexes 1 and 2, but not for complex 4. In conclusion, increased energy wasting measured in liver mitochondria from rats with cancer cachexia is dependent on cardiolipin but independent of ANT. Interactions between ANT and cardiolipin are modified when cancer cachexia occurs.

Predictors of changes in physical, psychosocial, sexual quality of life, and comfort with food after obesity surgery: a 12-month follow-up study.

PURPOSE: Although obesity surgery provides significant postoperative improvement in quality of life (QoL), it is still unclear which factors might predict improvement in QoL after surgery. We aimed to determine which factors might predict changes in physical, psychosocial, sexual QoL, and comfort with food 12 months after surgery, by putting to the test a QoL model based on Wilson and Cleary's model. METHODS: We included 126 obese patients (48.4% had gastric banding, 34.1% had sleeve gastrectomy, and 17.5% had gastric bypass). At baseline, we assessed QoL (Quality of Life, Obesity and Dietetics rating scale), BMI, depression (Beck Depression Inventory), and binge eating (Bulimic Investigatory Test, Edinburgh). At 12 months, we assessed QoL and BMI. To determine the predictors for changes in each QoL dimension after surgery, we used linear mixed models adjusted for preoperative age, BMI, time, type of surgery, preoperative binge eating severity, and preoperative depression severity. RESULTS: After 12 months, we found significant improvement in physical, psychosocial, sexual QoL, but not in comfort with food. Increased weight loss was associated with better improvement in physical and psychosocial QoL. Higher preoperative depression severity predicted poorer improvement in physical, psychosocial, and sexual QoL. Higher preoperative binge eating severity predicted poorer improvement in psychosocial, sexual QoL, and comfort with food. CONCLUSIONS: In addition to weight loss, preoperative levels of binge eating and depression should be considered as important predictors for QoL changes after bariatric surgery. Screening and treatment for preoperative depression and binge eating might improve QoL after bariatric surgery.

DHA effect on chemotherapy-induced body weight loss: an exploratory study in a rodent model of mammary tumors.

Body weight loss during the course of cancer disease has been associated with poor prognosis. Beside cancer-associated cachexia, weight loss can also result from chemotherapy. This work explored whether a model of mammary tumors in female Sprague Dawley rats could be appropriate to study the effect of doxorubicin on body weight, described weight change in this model, and assessed the effect of DHA on weight during chemotherapy. After tumor induction, rats were randomly assigned to a control or a DHA-enriched diet, and treated with doxorubicin or placebo twice a week for 2.5 wk (n = 6 in each group). Body weight, food intake, and tumor growth were monitored. Neither the induction of tumors nor their initial development impaired body weight gain. No reduction in food intake was observed. Tumor growth was similar between groups from day 1 to day 11. Although doxorubicin induced body weight loss from day 4 compared to placebo (P< 0.01) in rats fed the control diet, it did not induce body weight loss in rats fed the DHA-enriched diet (P = 0.02), indicating that DHA had a protective effect. These results indicate that doxorubicin can induce body weight loss in this model and that a DHA-enriched diet can prevent this effect.

High preoperative depression, phobic anxiety, and binge eating scores and low medium-term weight loss in sleeve gastrectomy obese patients: a preliminary cohort study.

OBJECTIVE: Although depression, anxiety, and binge eating are prevalent in candidates for bariatric surgery, their impact on weight loss is unknown following sleeve gastrectomy. This study assesses the associations between weight loss and preoperative depression, anxiety, and binge eating scores in patients undergoing sleeve gastrectomy for morbid obesity. METHOD: This cohort study included 34 patients who underwent sleeve gastrectomy for morbid obesity between May 2006 and February 2010 in a French tertiary referral center. We assessed preoperative depression (using the Beck depression inventory and the SCL-90-R depression subscale), anxiety (using the Hamilton anxiety rating scale and the SCL-90-R anxiety subscales), and binge eating (using the bulimic investigatory test, Edinburgh). The primary outcome was the percentage of excess weight loss at 12 months (PEWL). RESULTS: The preoperative mean body mass index (BMI) was 55.3 kg/m2 ± 10.2 kg/m2 and 41.7 kg/m2 ± 8.7 kg/m2 at the 12-month follow-up visit. The mean PEWL was 46.8% ± 15.8%. After adjusting for the preoperative BMI, the PEWL was negatively associated with preoperative scores for depression (ß= -0.357; P < 0.05), phobic anxiety (ß = -0.340; P < 0.05), interpersonal sensitivity (ß = -0.328; P < 0.05), and binge eating (ß = -0.315; P = 0.05). Other forms of anxiety were not correlated with the PEWL. CONCLUSIONS: Higher preoperative depression, phobic anxiety, interpersonal sensitivity, and binge eating scores are associated with low postoperative weight loss in patients undergoing sleeve gastrectomy. Future studies should assess the preoperative prevalence of syndromal or subsyndromal atypical depression and its relationship to postoperative weight loss in bariatric surgery candidates.

Efficiency of oxidative phosphorylation in liver mitochondria is decreased in a rat model of peritoneal carcinosis.

BACKGROUND & AIMS: Cancer cachexia is a dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism. The mechanisms leading to hypermetabolism are not totally elucidated. This study examines the efficiency of oxidative phosphorylation and energy wasting in liver mitochondria isolated from rats with cancer cachexia induced by peritoneal carcinosis (PC). METHODS: PC was generated by an intraperitoneal injection of cancer cells (PROb) in BDIX rats. The efficiency of oxidative phosphorylation and energy wasting as well as the role played by reactive oxygen species (ROS) and cardiolipin (mitochondrial inner membrane phospholipid) in these processes were assessed in liver mitochondria of PC and pair-fed control rats. RESULTS: The efficiency of oxidative phosphorylation decreased (-26%) while energy wasting increased (+22%) in liver mitochondria from PC compared to control rats. The increased energy wasting was associated with a higher cardiolipin content (+55%, p<0.05; R(2)=0.64, p<0.05) and with a lower n-6/n-3 polyunsaturated fatty acid ratio in cardiolipin (-45%, p<0.05; R(2)=0.21, p<0.05) in PC rats. ROS production was increased by 12-fold in liver mitochondria from PC rats. CONCLUSIONS: The efficiency of ATP synthesis was reduced and energy wasting processes were increased in liver mitochondria of PC rats. This suggests that liver mitochondria from PC rats request more nutrients than liver mitochondria from control rats to maintain the same ATP production. These alterations were associated to the content and fatty acid composition of cardiolipin.

n-3 PUFA-enriched diet delays the occurrence of cancer cachexia in rat with peritoneal carcinosis.

The aim of this study was to evaluate the effects of a fish oil (FO) diet (rich in long chain, n-3, polyunsaturated fatty acid) on cancer cachexia symptoms in rats. To this end, peritoneal carcinosis (PC) was generated by an intraperitoneal injection of cancer cells in BDIX rats fed FO or standard (Std) diets. Food intake and body weight were recorded throughout the study until sacrifice. PC rats were sacrificed when food intake was significantly and severely reduced. Fat and skeletal muscles masses were weighed and serum inflammatory cytokines concentration measured at sacrifice. Occurrence of anorexia in PC rats was delayed in the FO diet group (median time was multiplied by 2.5) in comparison with Std diet. At the time of sacrifice, PC rats displayed a lower body weight gain as well as lower muscle and fat masses than pair-fed rats, suggesting the presence of a hypermetabolism state. Serum TNF-alpha was significantly increased in PC rats compared with controls rats. There was no effect of FO diet on tissue mass (skeletal muscle and fat) or on TNF-alpha concentration. In conclusion, FO diet delays the appearance of anorexia induced by PC in rats.

Preoperative Chemerin Level Is Predictive of Inflammatory Status 1 Year After Bariatric Surgery.

BACKGROUND: Obesity is associated with chronic low-grade inflammation, which has been linked to increased morbidity. However, inflammation variably and unpredictably improves after bariatric surgery. This study aimed at (1) evaluating the relationship between amplitude of weight loss and variation of inflammatory parameters after bariatric surgery, and (2) identifying, among clinical and biological baseline parameters, predictive factors of variation in inflammatory parameters. METHODS: In a prospective cohort of patients who underwent bariatric surgery, serum concentrations of interleukin (IL)-6, IL-10, resistin, leptin, adiponectin chemerin, and C-reactive protein (CRP) were measured preoperatively and 1 year after surgery, and routine clinical and biochemical parameters were retrieved. Univariate and multivariate analyses (partial least square method) were performed to assess how parameters were associated with weight loss and to predict improvement of inflammatory parameters. RESULTS: Eighty-seven patients were included (mean weight ± SD 136.3 ± 3.2 kg, 35 gastric bypasses, 52 sleeve gastrectomies). In parallel with weight loss (39.5 ± 13.8 kg), pro-inflammatory markers (IL-6, CRP, leptin, resistin) significantly decreased, and anti-inflammatory markers (IL-10, adiponectin) increased. Multivariate analysis revealed a significant association between weight loss and improvement in inflammatory parameters. Among all the clinical and biological preoperative parameters, baseline chemerin level was the only parameter that was significantly associated with global improvement of the inflammatory status after surgery. CONCLUSION: The amplitude of weight loss 1 year after bariatric surgery was strongly correlated with improvement of inflammatory profile, which could be predicted by baseline plasma level of chemerin. This suggests a key role of chemerin in obesity-driven inflammation, and a potential use as a biomarker.

The lipidome as a composite biomarker of the modifiable part of the risk of breast cancer.

The potential for dietary fat to prevent breast cancer makes identification of defined molecules a mandatory step. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, we have used the fatty acid composition of white adipose tissue as biomarker of past lipid intake. When considered separately, candidate fatty acids identified as favourable on the basis of their association with breast cancer risk have usually led to inconsistent results in dietary intervention studies carried out in rats. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions, which finally determines the lipidome, the lipid profile that is found in individuals. We reappraised the role of the complete lipid profile through a comprehensive study of adipose tissue fatty acids obtained in patients with benign or malignant breast tumors. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low n-6/n-3 fatty acid ratio was associated with decreased breast cancer risk. The lipidome may provide the opportunity to quantify the modifiable part of the risk of breast cancer. The lipidome may be used as a template for designing proper dietary modifications in order to delay the occurrence of breast cancer. Which dietary modifications should be undertaken in order to bring a pertinent change to the lipidome with respect to the risk of breast cancer is currently unknown. The lipidome may allow the individualization of a high risk population of women, who may be targeted for a dietary prevention of breast cancer. The setting and validation of a high-throughput lipidomic station with analytical capabilities fitted to the need of mass screening is required. These two locks must be resolved before a primary prevention of breast cancer by diet could be contemplated.

Gut emptying affects dietary fat contribution to postprandial lipemia following sequential meals in healthy subjects.

OBJECTIVE: The present study examined the kinetic of plasma triacylglycerol (TAG) and gut emptying after sequential ingestion of breakfast and lunch, and the contribution of dietary fat ingested at breakfast to subsequent TAG after lunch. METHODS: Nine subjects ingested a breakfast (0730 h) and a lunch (1200 h) containing 25 and 44 g of fat, respectively. [1-(13)C] palmitate was added in breakfast only. Plasma TAG and chylomicron-TAG (CM-TAG) concentrations and [1-(13)C] palmitate enrichment were sequentially measured. On a consecutive day, an identical breakfast labeled with (123)I-Lipiodol was ingested, followed by a lunch for three controls. (123)I-Lipiodol dynamics was followed in vivo by scintigraphic imaging focused on the stomach, small bowel, and thoracic duct arch. RESULTS: An early rise in plasma and CM-TAG was observed after lunch ingestion. After breakfast, [1-(13)C] palmitate enrichment was maximal 150 and 210 min in plasma TAG and CM-TAG, respectively, decreased thereafter, and increased rapidly (50 min for plasma TAG and 30 min for CM-TAG) after lunch ingestion. Scintigraphic imaging appeared to show that fat ingested at breakfast was retained in part within the gut at lunch time. For the three subjects who ingested a lunch, a decrease of activity in the stomach and small bowel and a tendency for increased activity in the thoracic arch were observed. CONCLUSION: Contribution of fat ingested at breakfast to lipemia after lunch is confirmed. Fat ingested at breakfast was partly retained within the gut and was mobilized after lunch ingestion, as assessed by acceleration of gut emptying and thoracic duct flow after lunch.

NutriCancer: A French observational multicentre cross-sectional study of malnutrition in elderly patients with cancer.

OBJECTIVES: To compare the prevalence of malnutrition and nutritional management between elderly (≥70years old) and younger patients (<70years) with cancer. PATIENTS AND METHODS: This is a post-hoc analysis of NutriCancer 2012 study; a one-day cross-sectional nationwide survey conducted to assess malnutrition in adult patients with cancer in France. Patients diagnosed with cancer at the study date in both inpatient and outpatient settings were included. Data collection was performed by means of questionnaires completed by the physician, the patient and the caregiver. RESULTS: This post-hoc analysis compared 578 elderly patients (27.6%) vs. 1517 younger patients (72.4%). There were significant differences in cancer localization between the groups particularly in gastrointestinal cancer (27% in younger patients vs. 42% in elderly), breast cancer (17% vs 8% in elderly) and oropharyngeal (15% vs. 9% in elderly). Weight loss was significantly more reported in the elderly than in younger patients (73.6% vs. 67.6%, p=0.009). Elderly patients were more frequently malnourished than younger patients (44.9% vs. 36.7%, p=0.0006). Food intake was comparable between the groups; however, physicians overestimated the food intake, particularly in the elderly. The malnutrition management was more frequently proposed in elderly, as dietary advice and oral nutritional supplements, than in younger patients; however, enteral nutrition was significantly less undertaken in the elderly. CONCLUSION: Malnutrition is prevalent in elderly patients with cancer, and more frequent than in younger patients. There is a need for an early integration of the nutritional counselling in patients with cancer, and particularly in the elderly.