Late evening snack: Exploiting a period of anabolic opportunity in cirrhosis

Tsien, Cynthia; McCullough, Arthur J.; Dasarathy, Srinivasan

doi:10.1111/j.1440-1746.2011.06951.x

Cited by 214 publications

(200 citation statements)

References 71 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…Cirrhosis is a state of accelerated starvation and is associated with a number of metabolic perturbations, including increased blood ammonia concentration (47). The present studies provide a potential mechanistic link involving autophagy between two Fig.…”

Section: Discussionmentioning

confidence: 85%

“…It is responsible for controlled degradation of cytoplasmic components, including damaged organelles/toxic protein aggregates, as well as providing essential nutrients during starvation and stress to maintain cellular homeostasis (2). Since cirrhosis is a state of accelerated starvation (6,47), enhanced muscle autophagy may serve as a source of essential amino acids for critical cellular function.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

Qiu¹,

Tsien

Thapalaya³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

176

226

View full text Add to dashboard Cite

SV, Dasarathy S. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 303: E983-E993, 2012. First published August 14, 2012; doi:10.1152/ajpendo.00183.2012.-Hyperammonemia and sarcopenia (loss of skeletal muscle) are consistent abnormalities in cirrhosis and portosystemic shunting. We have shown that muscle ubiquitin-proteasome components are not increased with hyperammonemia despite sarcopenia. This suggests that an alternative mechanism of proteolysis contributes to sarcopenia in cirrhosis. We hypothesized that autophagy could be this alternative pathway since we observed increases in classic autophagy markers, increased LC3 lipidation, beclin-1 expression, and p62 degradation in immunoblots of skeletal muscle protein in cirrhotic patients. We observed similar changes in these autophagy markers in the portacaval anastamosis (PCA) rat model. To determine the mechanistic relationship between hyperammonemia and autophagy, we exposed murine C2C12 myotubes to ammonium acetate. Significant increases in LC3 lipidation, beclin-1 expression, and p62 degradation occurred by 1 h, whereas autophagy gene expression (LC3, Atg5, Atg7, beclin-1) increased at 24 h. C2C12 cells stably expressing GFP-LC3 or GFPmCherry-LC3 constructs showed increased formation of mature autophagosomes supported by electron microscopic studies. Hyperammonemia also increased autophagic flux in mice, as quantified by an in vivo autophagometer. Because hyperammonemia induces nitration of proteins in astrocytes, we quantified global muscle protein nitration in cirrhotic patients, in the PCA rat, and in C2C12 cells treated with ammonium acetate. Increased protein nitration was observed in all of these systems. Furthermore, colocalization of nitrated proteins with GFP-LC3-positive puncta in hyperammonemic C2C12 cells suggested that autophagy is involved in degradation of nitrated proteins. These observations show that increased skeletal muscle autophagy in cirrhosis is mediated by hyperammonemia and may contribute to sarcopenia of cirrhosis.

show abstract

Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

Qiu¹,

Tsien

Thapalaya³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

176

226

View full text Add to dashboard Cite

show abstract

“…16,[23][24][25] Late evening supplementation as well has been recently reviewed and has shown promise as being superior to daytime supplementation in patients with cirrhosis. 17,19,22 In conclusion, although there is insufficient evidence to definitively state that the oro-enteral supplementation of macro and micronutrients impacts outcomes, the meta-analysed data are suggestive that there is the potential for clinical benefit without an increase in adverse events. Adequately powered and likely multicentre studies will be needed to clarify the impact on relevant clinical outcomes (mortality, hepatic function, quality of life and muscle mass and muscle function as measured by gold-standard techniques).…”

Section: Discussionmentioning

confidence: 95%

“…The latter is considered a limitation as BCAA supplements may have unique pathophysiological properties and are not routinely available. 17 Therefore, the practising clinician is left without a clear strategy for the management of malnutrition in cirrhosis. In keeping with this uncertainty, cirrhosis-specific guidelines for supplementation via the oral route or by an enteral feeding tube (herein also termed oro-enteral supplementation), are predominantly based on grade C evidence (expert opinions and/or clinical experience).…”

Section: Discussionmentioning

confidence: 99%

Meta‐analysis: oral or enteral nutritional supplementation in cirrhosis

Ney

Vandermeer

Zanten

et al. 2013

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…However, positive benefits were noted in improved fuel metabolism in short-term studies and increases in lean body mass in long term studies. The review did attempt to determine the optimal caloric intake of supplements, but did not review protein content of the supplements or age of the subjects [71] , making it difficult to draw conclusions regarding evening supplementation in older adults. A summary of studies providing late evening or overnight supplementation to older adults (average age >60) with cirrhosis can be found in table 2.…”

Section: Iiames J Et Al Protein In Older Cirrhotic Adultsmentioning

confidence: 99%

Protein Recommendations for Older Adults with Cirrhosis: A Review

Iiames

Logomarsino

2015

Journal of Gastroenterology and Hepatology Research

View full text Add to dashboard Cite

Protein intake has a key role in liver cirrhosis in older adults. However, types and amounts of protein intake in cirrhosis have been controversial. The aim of this paper is to investigate the optimal protein intake for management of cirrhosis and prevention of hepatic encephalopathy in older adults. Protein restriction of 0.6 g/kg/d has traditionally been used as medical nutrition therapy in liver cirrhosis. However, recent evidence has shown that protein restrictions have many negative consequences for older adults with cirrhosis. Current research indicates protein intakes of 1.2-1.5 g/ kg/d in liver cirrhosis; however, many older adults do not consume this amount. Strategies to help increase protein intake and manage cirrhosis include ensuring adequate protein at every meal through either regular intake or supplementation, protein supplementation prior to bedtime or overnight, and supplementation with branchedchain amino acids. An emphasis on vegetable protein versus animal protein is probably not an advantageous treatment option because of lack of conclusive evidence regarding benefits and potential negative side effects. and progression of chronic liver disease and cirrhosis.There are several different factors that naturally occur in older adulthood that help contribute to the development of chronic liver disease and cirrhosis. After reaching maximum size in early adulthood, the liver steadily decreases in both size and the amount of blood flow it receives, leading to decreased function and efficiency over time [10] . Also, increased ammonia production and bacterial overgrowth are common in older adulthood, both of which are thought to play a key role in development of hepatic encephalopathy [11] . Older adults tend to have chronic constipation, intestinal dysmotility, and increased colonic transit time, which predisposes them to increased ammonia production [12] . Finally, older adulthood is associated with a higher incidence of diabetes, which is strongly correlated to progression of liver cirrhosis [13] . Pathogenesis of malnutrition in older adults with cirrhosisIt is estimated that 20% of patients with compensated cirrhosis and 60% of patients with decompensated cirrhosis have malnutrition [14] . In older adults, protein energy malnutrition is associated with high health care costs, increased frequency of infection and bedsores, increased morbidity and mortality, and poor physical functioning [4,5] . In canine trials, poor nutritional status has been shown to encourage the development of hepatic encephalopathy [15] . In addition, malnutrition in cirrhosis is positively associated with old age [14] . Multiple factors help contribute to the development of malnutrition in older adults with cirrhosis, including inadequate intake, altered absorption, sarcopenia, and altered metabolism. All causes must be explored and taken into consideration when developing treatment and prevention strategies.In older adults, food intake naturally decreases over time [16] , which promotes the development of malnutri...

show abstract

Late evening snack: Exploiting a period of anabolic opportunity in cirrhosis

Abstract: Late evening snack holds the most promise as an intervention to reverse anabolic resistance and sarcopenia of cirrhosis with improved quality of life in patients with cirrhosis. Long term benefit and improved survival need critical evaluation.

Cited by 214 publications

References 71 publications

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

Meta‐analysis: oral or enteral nutritional supplementation in cirrhosis

Protein Recommendations for Older Adults with Cirrhosis: A Review

Contact Info

Product

Resources

About