scholarly journals MMP12 knockout prevents weight and muscle loss in tumor-bearing mice

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lingbi Jiang ◽  
Mingming Yang ◽  
Shihui He ◽  
Zhengyang Li ◽  
Haobin Li ◽  
...  

Abstract Background Colorectal cancer is a malignant gastrointestinal cancer, in which some advanced patients would develop cancer cachexia (CAC). CAC is defined as a multi-factorial syndrome characterized by weight loss and muscle loss (with or without fat mass), leading to progressive dysfunction, thereby increasing morbidity and mortality. ApcMin/+ mice develop spontaneous intestinal adenoma, which provides an established model of colorectal cancer for CAC study. Upon studying the ApcMin/+ mouse model, we observed a marked decrease in weight gain beginning around week 15. Such a reduction in weight gain was rescued when ApcMin/+ mice were crossed with MMP12−/− mice, indicating that MMP12 has a role in age-related ApcMin/+-associated weight loss. As a control, the weight of MMP12−/− mice on a weekly basis, their weight were not significantly different from those of WT mice. Methods ApcMin/+; MMP12−/− mice were obtained by crossing ApcMin/+ mice with MMP12 knockout (MMP12 −/−) mice. Histological scores were assessed using hematoxylin-eosin (H&E) staining. MMP12 expression was confirmed by immunohistochemistry and immunofluorescence staining. ELISA, protein microarrays and quantitative Polymerase Chain Reaction (qPCR) were used to investigate whether tumor could up-regulate IL-6. Cell-based assays and western blot were used to verify the regulatory relationship between IL-6 and MMP12. Fluorescence intensity was measured to determine whether MMP12 is associated with insulin and insulin-like growth factor 1 (IGF-1) in vitro. MMP12 inhibitors were used to explore whether MMP12 could affect the body weight of ApcMin/+ mice. Results MMP12 knockout led to weight gain and expansion of muscle fiber cross-sectional area (all mice had C57BL/6 background) in ApcMin/+ mice, while inhibiting MMP12 could suppress weight loss in ApcMin/+ mice. MMP12 was up-regulated in muscle tissues and peritoneal macrophages of ApcMin/+ mice. IL-6 in tumor cells and colorectal cancer patients is up-regulation. IL-6 stimulated MMP12 secretion of macrophage. Conclusions MMP12 is essential for controlling body weight of Apc Min/+ mice. Our study shows that it exists the crosstalk between cancer cells and macrophages in muscle tissues that tumor cells secrete IL-6 inducing macrophages to up-regulate MMP12. This study may provide a new perspective of MMP12 in the treatment for weight loss induced by CAC.

2019 ◽  
Vol 34 (4) ◽  
pp. 873-878
Author(s):  
Tijana Serafimovska ◽  
Marija Darkovska Serafimovska ◽  
Milka Zdravkovska ◽  
Trajan Balkanov

Knowledge of the role of the endocannabinoid system in the modulation of immune functions, the influence of mood, the regulation of appetite, gives us the right to think about the possibility of use of cannabinoids for the treatment of cachexia. Cachexia, also known as weight loss syndrome, is a common problem in patients with human immunodeficiency virus (HIV). Weight loss syndrome is defined as a loss of at least 10% of the body weight. In HIV-positive patients, weight loss syndrome has been associated with chronic diarrhea, fatigue, and fever for at least 30 days. This serious situation leads to significant morbidity and mortality for these patients. The use of cannabinoids to improve appetite and regain weight in HIV-positive patients is recommended, but it is unclear whether they are truly safe and effective. MARINOL (dronabinol), 2.5, 5 or 10 mg tablets is the only synthetic cannabinoid (tetrahydrocannabinol (THC) isomer) intended for oral administration and FDA approved for two indications: treatment of anorexia associated with weight loss in people with acquired immune deficiency syndrome (or HIV-positive patients) and vomiting caused by chemotherapy in people whose nausea and vomiting have not improved with usual antiemetics. In the United States, Marinol is treated as a non narcotic drug with a very low risk of physical and mental dependence (categorized into level III of controlled substances). The dosage for treatment of weight loss depends on tolerability, from 1 x 2.5 mg /day to 2 x 10 mg /day. The medicine is stated to be taken before meals: before dinner when is administered once daily or before breakfast and dinner if the total dose is divided into twice daily intake. An online literature review published by June 2018 identified a total of six randomized clinical trials (RCTs) that were conducted to evaluate the effects of dronabinol for the treatment of cachexia in HIV-positive patients. They included a total of 298 patients. In 5 of the six studies conducted, the effects of dronabinol were compared with placebo, and in only one study the effects of dronabinol were compared with megestrol acetate. Only one of the six studies was classic placebo-controlled study that reported the effects of dronabinol on body weight correction, while in other studies the effects of dronabinol on body weight correction were secondary notification. This study is also the only study on which base indication for dronabinol are approved. Studies show that dronabinol at doses of 5mg /day stimulates weight gain compared with placebo. Dronabinol compared to megestrol showed a lack of effect. The conclusion of these studies, however, is that use of cannabinoids can have a positive effect on improving appetite and weight gain in HIV-positive patients.


2018 ◽  
Vol 16 (2) ◽  
pp. 201-210
Author(s):  
Muryanto Muryanto ◽  
Pita Sudrajad ◽  
Amrih Prasetyo

The aim of the study was to determine the development of ramie plants (Boehmeria nivea L. Gaud) and the effect of using ramie leaves on feed on the body weight gain of Wonosobo Sheep (Dombos). Research on the development of ramie plants using survey methods in the area of ramie plant development in Wonosobo Regency. While the research on the use of ramie leaves for fattening was carried out in Butuh Village, Kalikajar District, Wonosobo Regency in 2018. 21 male Dombos were divided into 3 feed treatments with forage proportions of 70%, 50% and 30 ramie leaves respectively. %. The results showed that currently ramie plants were being developed in Wonosobo Regency by CV. Ramindo Berkah Persada Sejahtera in Gandok Village, Kalikajar District, Wonosobo Regency, Central Java. Until now the area of the crop has reached 13 ha. Of this area will produce ramie leaves 195,000 kg / year. If one sheep needs 4 kg of ramie / tail / day leaves, then the potential capacity of sheep is 135 heads / year, if the given one is 50% then the Jurnal Litbang Provinsi Jawa Tengah, Volume 16 202 Nomor 2 – Desember 2018potential capacity is 270 heads / year and if it is reduced again to 25% of ramie leaves then the potential capacity 440 heads / year. The use of ramie leaves as a feed for Wonosobo Sheep fattening can be given as much as 30% in fresh form.


Author(s):  
P. M, Lunagariya ◽  
R. S. Gupta ◽  
S. V. Shah ◽  
Y. G. Patel

The study was planned to evaluate the effect of exogenous fibrolytic enzymes (EFE) supplementation for 56 days @ 240 mg/kg total mixed ration (TMR) on digestibility of dry matter and nutrients in dairy cows. Six dry non-pregnant cows were assigned in each treatment with and without EFE. The digestibility trial of seven days was conducted after 49 days of feeding. Dry matter and nutrients intake of cows was not influenced by EFE. The supplementation of EFE had improved digestibility of dry matter, organic matter, crude fiber, neutral detergent fiber, cellulose (p less than 0.01), as well as digestibility of nitrogen-free extract and acid detergent fiber, was also higher (pless than 0.05). The body weight gain of cows was higher on the supplementation of EFE in TMR. The study concluded that feeding exogenous fibrolytic enzymes (240 mg/kg) supplemented TMR improved digestibility of dry matter and nutrients, which was reflected as higher body weight gain in dry non-pregnant Gir and crossbred dairy cows.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1359
Author(s):  
Noga C Minsky ◽  
Dafna Pachter ◽  
Galia Zacay ◽  
Naama Chishlevitz ◽  
Miriam Ben-Hamo ◽  
...  

Since the outbreak of COVID-19, billions of people have gone into lockdown, facing pandemic related challenges that engender weight gain, especially in the obese. We report the results of an online survey, conducted during Israel’s first quarantine, of 279 adults treated in hospital-based obesity clinics with counseling, medications, surgery, endoscopic procedures, or any combination of these for weight loss. In this study, we assessed the association between changes in dietary and lifestyle habits and body weight, and the benefits of receiving weight management care remotely through telemedicine during lockdown. Compared to patients not receiving obesity care via telemedicine, patients receiving this care were more likely to lose weight (OR, 2.79; p = 0.042) and also to increase participation in exercise (OR, 2.4; p = 0.022). While 40% of respondents reported consuming more sweet or salty processed snacks and 33% reported less vegetables and fruits, 65% reported more homemade foods. At the same time, 40% of respondents reported a reduction in exercise and 52% reported a decline in mood. Alterations in these eating patterns, as well as in exercise habits and mood, were significantly associated with weight changes. This study highlights that lockdown affects health behaviors associated with weight change, and advocates for the use of telemedicine to provide ongoing obesity care during future quarantines in order to promote weight loss and prevent weight gain.


1985 ◽  
Vol 249 (2) ◽  
pp. R203-R208
Author(s):  
R. B. Melnyk ◽  
J. M. Martin

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Beatrice A Golomb ◽  
Hayley J Koslik ◽  
Alexis K Bui

Background and Goal: Sleep problems were significantly increased on simvastatin ( simva ) (but not pravastatin) vs placebo in the UCSD Statin Study. Sleep problems on simva predicted glucose rise. Weight gain has also been reported as a statin side effect. We sought to capitalize on existing data to assess whether sleep problems on simva related to weight gain in men. Method: 442 men without known diabetes or CVD were randomized to simva 20mg or placebo for 6 mon. One hundred eighty and 186 completed single-item self-rating of change in sleep problems vs baseline ( Δslpprob ). Weight (lb) was measured at baseline and 6 mon. Missing 6 mon values were imputed. Analyses: A. Regressions stratified by treatment assessed prediction of weight change by Δslpprob, adjusted for baseline weight. B. Regressions assessed prediction of weight change by the interaction term of simva (vs placebo) x Δslpprob, adjusted for the components of the interaction and baseline weight. Since age-related muscle loss may complicate weight change in elderly; and young adults have low vulnerability to metabolic problems, analyses were repeated excluding these groups. Results: A. Increased sleep problems on simva predicted weight gain (significant), but on placebo predicted weight loss (nonsignificant). B. The Δslpprob x simva interaction term significantly predicted weight gain. When that was parceled out, simva, outside of the sleep relationship, negatively predicted weight change. Exclusion of young adults and elderly strengthened significance of findings (Table). Discussion: Sleep problems, which differentially arise on simva, differentially predict weight gain on simva. This expands the metabolic effects to which sleep problems on simva may contribute and might possibly favor mediation by sleep apnea (a reported complication of simva). Once the sleep problem effect is considered, simva use predicted weight loss . The relative contribution of fat vs muscle loss (vs other) requires exploration.


Development ◽  
1962 ◽  
Vol 10 (4) ◽  
pp. 530-562
Author(s):  
M. Enesco ◽  
C. P. Leblond

While the organs and tissues of the young rat are known to increase in size with age (Donaldson, 1924), little is known of the role played by the component cells in this increase. There is evidence that cells enlarge (Levi, 1906; Plenk, 1911) and new cells are added (Strasburger, 1893), but we do not know to what extent the enlargement and proliferation of the cells cause the growth of organs and tissues. The present work is an attempt to clarify this problem. In the past, the growth of organs and tissues has often been measured by weight gain (Donaldson, 1924). However, this approach might be misleading, since the body-weight may increase in the absence of growth, for instance as a result of fat-storage in old rats, of pregnancy in females, and even of changes in room temperature.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Win Hlaing Than ◽  
Jack K C Ng ◽  
Gordon C K Chan ◽  
Winston Fung ◽  
Cheuk Chun Szeto

Abstract Background and Aims The prevalence of obesity has increased over the past decade in patients with End Stage Kidney Disease (ESKD). Obesity at the initiation of peritoneal dialysis (PD) was reported to adversely affect clinical outcomes. However, there are few studies on the prognostic relevance of weight gain after PD. Method We reviewed the change in body weight of 954 consecutive PD patients from the initiation of dialysis to 2 years after they remained on PD. Clinical outcomes including patient survival, technique survival, and peritonitis rate in the subsequent two years were reviewed. Results The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men and 504 (52.8%) had diabetes. After the first 2 years on PD, the average change in body weight was 1.2± 5.1 kg; their body weight was 63.0 ± 13.3 kg; body mass index (BMI) 24.4 ± 4.4 kg/m2. The patient survival rates in the subsequent two years were 64.9%, 75.0%, and 78.9% (log rank test, p = 0.008) for patients with weight loss ≥3 kg during the first 2 years of PD weight change between -3 and +3 kg, and weight gain ≥3 kg, respectively. The corresponding technique survival rates in the subsequent two years were 93.1%, 90.1%, 91.3%, respectively (p = 0.110), and the peritonitis rates were 0.7±1.5, 0.6±1.7, and 0.6±1.1 episodes per patient-year, respectively (p = 0.3). When the actual BMI after the first 2 years of PD was categorized into underweight, normal weight, marginal overweight, overweight, and obesity groups, the patient survival rates in the subsequent two years were 77.3%, 75.2%, 73.3%, 74.3%, and 75.9%, respectively (p= 0.005), and technique survival 98.0%, 91.9%, 88.0%, 92.8%, and 81.0%, respectively (p= 0.001). After adjusting for confounding clinical factors by multivariate Cox regression models, weight gain ≥ 3kg during the first 2 years of PD was an independent protective factor for technique failure (adjusted hazard ratio [AHR] 0.049; 95% confidence interval [CI] 0.004-0.554, p = 0.015), but was an adverse predictor of patient survival (AHR 2.338, 95%CI 1.149-4.757, p = 0.019). In contrast, weight loss ≥ 3kg during the first 2 years of PD did not predict subsequent patient or technique survival. Conclusion Weight gain during the first 2 years of PD confers a significant risk of subsequent mortality but appears to be associated with a lower risk of technique failure. The mechanism of this discordant risk prediction deserves further study.


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