Methionine restriction (MR) prevents obesity because of a futile lipid cycle in which two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. In this study, we show that MR promotes weight loss not just by this futile lipid cycle, but also by a coordinated response that involves apoptosis (normal cell death) and autophagy (a metabolic process by which the body consumes its own tissue) to maintain physiological equilibrium.
It has been observed that the hormones adiponectin and fibroblast growth factor 21 are consistently elevated during MR. To clearly define the roles of ADIPOQ and FGF21 during MR, we used mice that lacked either or both hormones. The obese mice, once placed on an MR diet, lost weight regardless of the presence of these hormones, demonstrating that neither is essential to reduce fat during MR.
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Cooke, D., Mattocks, D., Nichenametla, S. N., Anunciado‐Koza, R. P., Koza, R. A., & Ables, G. P. (2020). Weight Loss and Concomitant Adipose Autophagy in Methionine‐Restricted Obese Mice is Not Dependent on Adiponectin or FGF21. Obesity.
Despina Komninou, Virginia L. Malloy, Jay A. Zimmerman, Raghu Sinha, John P. Richie Jr.
GeroScience. 2020 Feb
Dietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in 87% CF rats and CPN in 62% of CF animals, no evidence of kidney disease was observed in MR rats. Consistent with the absence of renal pathology, urinary albumin levels were lower in the MR group compared to controls throughout the study, with over a six-fold difference between the groups at 30 months of age. Biomarkers associated with renal disease, namely, clusterin, cystatin C, and β-2 microglobulin, were reduced following 18 months of MR. A reduction in testicular tumor incidence from 88% in CF to 22% in MR rats was also observed. These results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases.
A new epidemiological study published in The BMJ explores the association between eating red meat and the risk of death, specifically how risk of death can be lessened through dietary change—decreasing red meat consumption while increasing intake of healthier animal and plant-based foods. This correlates with OFAS research in rodents demonstrating that a sulfur amino acid-restricted (SAAR) diet can increase lifespan and delay onset of age-related diseases. In general, meat and other animal-based food sources have high SAA while plant-based food sources such as vegetables, legumes, whole grains, and fruits have low SAA.
The study looked to produce evidence backing previous studies showing “that higher red meat consumption, especially processed red meat, is associated with an increased risk of type 2 diabetes, cardiovascular disease, certain types of cancer, including colorectal cancer, and mortality.” Analyzing data from a cohort of 81,469 US health professionals (male and female) from a 16-year period, this study found 1) increases in red meat consumption, especially processed meat, are associated with a higher risk of death and 2) decreases in red meat consumption and simultaneous increases in healthy alternative food choices over time are associated with a lower mortality risk, further supporting the health benefits of replacing red and processed meat with healthy protein sources, whole grains, or vegetables.
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Zheng Yan, Li Yanping, Satija Ambika, Pan An, Sotos Prieto Mercedes, Rimm Eric et al. Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studiesBMJ 2019; 365 :l2110