Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization

MacArthur, Michael R.; Mitchell, Sarah J.; Chadaideh, Katia S.; Treviño-Villarreal, J. Humberto; Jung, Jonathan; Kalafut, Krystle; Reynolds, Justin S.; Mann, Charlotte G.; Trocha, Kaspar; Tao, Ming; Cho, Tay Zar Aye; Koontanatechanon, Anantawat; Yeliseyev, Vladimir; Bry, Lynn; Longchamp, Alban; Ozaki, C. Keith; Lewis, Caroline A.; Carmody, Rachel N.; Mitchell, James R.

doi:10.1016/j.celrep.2022.111187

Cited by 8 publications

(21 citation statements)

References 72 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To keep diets isocaloric, the reduction of dietary amino acids from the Low AA diet was balanced by addition of carbohydrates, and the reduction of isoleucine from the Low Ile diet was balanced with non-essential amino acids. The protein to carbohydrate ratio, the type of dietary carbohydrate consumed, the precise degree of restriction, the specific non-essential amino acids added to the Low Ile diet, and diet-induced changes to the microbiome could all play a role in the responses we observe here (MacArthur et al, 2022;Pak et al, 2019;Solon-Biet et al, 2014;Solon-Biet et al, 2015;Wali et al, 2021). Finally, our molecular analysis was largely limited to the liver, and while this is the first organ to be exposed to absorbed nutrients, dietary isoleucine metabolism occurs in many tissues (Neinast et al, 2019).…”

Section: Limitations Of Studymentioning

confidence: 91%

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice

Green

Murphy

Babygirija

et al. 2022

Preprint

View full text Add to dashboard Cite

Low protein (LP) diets promote health and longevity in diverse species. Although the precise components of an LP diet that mediate its beneficial effects have not been defined, reducing dietary levels of the three branched-chain amino acids (BCAAs) leucine, isoleucine and valine promotes metabolic health in both sexes, and increases lifespan while reducing frailty in male, but not female, C57BL/6J mice. Each BCAA has unique metabolic effects, and we recently showed that restriction of isoleucine is both sufficient to promote metabolic health and required for the metabolic benefits of an LP diet in male C57BL/6J mice. Here, we tested the hypothesis that specifically restricting isoleucine could promote healthy aging in genetically heterogenous UM-HET3 mice. We find that a reduced isoleucine diet improves the metabolic health of both young and old HET3 mice, promoting leanness and glycemic control. Restriction of isoleucine starting in adult, 6 month old HET3 mice reprograms hepatic metabolism in a way distinct from an LP diet. Finally, we find that a reduced isoleucine diet reduces frailty and extends the lifespan of both male and female HET3 mice, but to a much greater degree in males. Our results demonstrate that restricting dietary isoleucine can increase health span and longevity in a genetically diverse population of mice, and suggests that reducing dietary levels of isoleucine may have great potential as a geroprotective intervention.

show abstract

Section: Limitations Of Studymentioning

confidence: 91%

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice

Green

Murphy

Babygirija

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Carbohydrate-loading drinks were modeled using a 50% (w/w) sucrose-water solution, hereafter referred to as “high carbohydrate - HC”. The choice of sucrose as the source of carbohydrate was based on the following rationale: 1) Dietary protein restriction benefits have been achieved by substituting protein with sucrose 24 , 41 . 2) Metabolic outcomes of low (10%)-protein, high (70%)-carbohydrate diets are worse when carbohydrates comprise a mixture of monosaccharides fructose and glucose 28 .…”

Section: Resultsmentioning

confidence: 99%

Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21

Agius,

Emsley,

Lyon

et al. 2024

Nat Commun

Self Cite

View full text Add to dashboard Cite

Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21.

show abstract

“…Another layer of complexity stems from the differential effects of LPD on specific amino acids (AAs) in the liver [ 85 ]. For instance, LPD is linked to a selective increase in the hepatic levels of aspartate, serine, and glutamate, along with a significant reduction in other AAs.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, LPD is linked to a selective increase in the hepatic levels of aspartate, serine, and glutamate, along with a significant reduction in other AAs. This is intriguing as it challenges the conventional belief that protein restriction uniformly enhances ATF4-activated non-essential amino acid biosynthetic genes [ 85 ]. Methionine restriction, a form of LPD, has been studied for its beneficial impact on cancer therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

Golonko,

Pienkowski,

Swislocka

et al. 2024

Cell Death Dis

View full text Add to dashboard Cite

Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, in the context of immunotherapy, there is the potential for the immune system to either support or hinder the administered treatment. This review encompasses recent and pivotal studies that assess the influence of dietary elements, including vitamins, fatty acids, nutrients, small dietary molecules, dietary patterns, and caloric restriction, on the ability to modulate immune responses. Furthermore, the article underscores how these dietary factors have the potential to modify and enhance the effectiveness of anticancer immunotherapy. It emphasizes the necessity for additional research to comprehend the underlying mechanisms for optimizing the efficacy of anticancer therapy and defining dietary strategies that may reduce cancer-related morbidity and mortality. Persistent investigation in this field holds significant promise for improving cancer treatment outcomes and maximizing the benefits of immunotherapy.

show abstract

Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization

Cited by 8 publications

References 72 publications

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice

Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21

Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

Contact Info

Product

Resources

About