Weight Loss and Concomitant Adipose Autophagy in Methionine-Restricted Obese Mice is Not Dependent on Adiponectin or FGF21

Weight Loss and Concomitant Adipose Autophagy in Methionine-Restricted Obese Mice is Not Dependent on Adiponectin or FGF21

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.

Scientifically-designed fasting diet reduces risks for aging diseases

Scientifically-designed fasting diet reduces risks for aging diseases

carrot-kale-walnuts-tomatoesIf you could lose weight and reduce your risk of life-threatening disease by dieting five days every few months, would you do it?

A recent study conducted by researchers at the University of Southern California Leonard Davis School of Gerontology, demonstrated a host of benefits. They placed 100 generally healthy participants into two study arms to test the effects of a fasting-mimicking diet—low in calories, sugars, and protein, but high in unsaturated fats. The diet proved to have significant effects on markers/risk factors associated with aging and age-related diseases.

According to the findings, the diet reduced the study participants’ risks for cancer, diabetes, heart disease, and other age-related diseases. It also shrank waistlines and resulted in weight loss, both in total body fat and trunk fat, but did not reduce muscle mass. The researchers noted that participants considered “at risk” because they had risk factors (high IGF (Insulin-like Growth Factor)-1, cholesterol, blood pressure, or blood sugar levels) made significant progress toward better health. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases.

“This study provides evidence that people can experience significant health benefits through a periodic, fasting-mimicking diet that is designed to act on the aging process,” said Valter Longo, director of the USC Longevity Institute and a professor of biological sciences for USC Davis and Dornsife College of Letters, Arts and Sciences. “Prior studies have indicated a range of health benefits in mice, but this is the first randomized clinical trial with enough participants to demonstrate that the diet is feasible, effective and safe for humans. Larger FDA studies are necessary to confirm its effects on disease prevention and treatment.”¹

The next step for researchers is a large phase III clinical trial, which compares new treatments to what is already available. This trial will test the fasting-mimicking diet on patients diagnosed with age-related diseases or at high risk for them.


¹Gersema E. Scientifically-designed fasting diet lowers risks for major diseases. Press Room. https://pressroom.usc.edu/scientifically-designed-fasting-diet-lowers-risks-for-major-diseases/. Published February 15, 2017.

Bone-Derived Hormone Suppresses Food Intake

Bone-Derived Hormone Suppresses Food Intake

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We often think of bones as immobile structures, but scientists are learning that bones are far more dynamic than once believed. Research has shown that they play important roles in immunity, kidney health, and metabolism. In a recent study, Dr. Stavroula Kousteni, Associate Professor at Columbia University Medical Center, led her team to the discovery that lipocalin 2, a hormone secreted by bone cells, suppresses appetite in mice. The study findings will potentially add to the understanding of weight management and maintaining a healthy metabolism and also raise questions about the possibility of other bone-derived hormones and what their potential functions could be.

Previously, it was thought that lipocalin 2 was only secreted by adipose tissue and contributed to obesity. Using genetically modified mice, Dr. Kousteni and her team showed lipocalin 2 levels were tenfold higher in osteoblasts (the bone forming cells) versus fat.  In mice that were engineered to lack lipocalin 2 in fat cells or osteoblasts, the investigators found that only mice lacking lipocalin 2 in the osteoblasts had increased food intake, body weight, and impaired glucose metabolism. In normal mice and in obese leptin-receptor deficient mice, administration of lipocalin 2 suppressed appetite, decreased body weight and improved glucose metabolism.

The brain controls feeding behavior. The Kousteni team demonstrated that lipocalin 2 crosses the blood-brain barrier and binds to the melanocortin 4 receptor, (which is linked to feeding behavior) in the neurons of the hypothalamus, thereby activating appetite-suppressing pathways in the brain. This shows at least in mice, that control of appetite is, in part, an endocrine function of the bone. The study findings could lead to the development of new treatments for obesity, type 2 diabetes, and other metabolic disorders. Interestingly, type ll diabetic patients with higher lipocalin 2 levels had lower body weight and glycated hemoglobin levels, the latter being a measure of glucose control.

“In recent years, studies at CUMC and elsewhere have shown that bone is an endocrine organ and produces hormones that affect brain development, glucose balance, kidney function, and male fertility,” says Dr. Kousteni. “Our findings add a critical new function of bone hormones to this list—appetite suppression—which may open a wholly new approach to the treatment of metabolic disorders.”¹


¹ “Bone-Derived Hormone Suppresses Appetite in Mice.” Columbia University Medical Center Newsroom. Columbia University Medical Center, 08 Mar. 2017. Web.