Modulation of nutrient sensing nuclear hormone receptors promotes weight loss through appetite suppression in mice.

AIM: Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in glucose and lipid metabolism. Three isoforms of PPARs have been identified with different tissue distribution and biological functions. Although the pharmacology of each receptor is well studied, the physiological effect of simultaneous activation of PPARalpha, gamma and delta is only starting to emerge. We sought to determine the biological effects of a novel PPAR pan activator and elucidate the physiological mechanisms involved. METHODS: Ob/ob, diet-induced obese (DIO) or PPARalpha knockout mice were administered a novel agonist that activates all PPARs to various degrees to determine the effect on body weight, body composition, food intake and energy expenditure. In addition, serum parameters including glucose, insulin, triglycerides and ketone bodies as well as tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and skeletal muscle histopathology was also studied. RESULTS: We report that simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist treatment increased lipid oxidation, although appetite suppression was mainly responsible for the weight loss. Agonist-induced weight loss was completely absent in PPARalpha knockout mice suggesting that PPARalpha pharmacology was the major contributor to weight regulation in mice. CONCLUSIONS: Our work provides evidence that simultaneous activation of PPARalpha, gamma and delta decreases body weight by regulating appetite. These effects of the pan agonist were completely absent in PPARalpha knockout mice, suggesting that PPARalpha pharmacology was the major contributor to weight loss.

Position of the American Dietetic Association: liberalized diets for older adults in long-term care.

Malnutrition, weight loss, and resident satisfaction are serious issues that need to be addressed by dietetics professionals working in long-term-care facilities. Medical nutrition therapy for older adults in long-term care is multifaceted and critical to reducing the risks of malnutrition and weight loss. To meet the needs of every resident, dietetics professionals must consider each person holistically, including personal goals, overall prognoses, benefits and risks of treatment, and perhaps most important, quality of life. For some long-term-care residents the use of liberalized diets, when appropriate, can enhance both quality of life and nutritional status, thus increasing the resident's satisfaction with the meals provided and reducing the risks of malnutrition and weight loss.