Collins 2017 MiPschool Obergurgl
Event: MiPschool Obergurgl 2017
Nonhuman primates can serve as useful models for human disease. Specifically, cynomolgus macaques (Macaca fascicularis) are well suited to model long-term dietary changes . Similar to humans, these animals exhibit similar risk factors for developing disease, such as: concentrations of circulating lipids, blood pressure, obesity, and inflammation.  A western diet has been associated with increased incidences of obesity, cardiovascular disease, hypertension, type 2 diabetes, and hypercholesterolemia.  Conversely, a mediterranean diet has been associated with lower risk of cardiometabolic disease by improvement of insulin resistance, lipid levels, blood pressure, and inflammation. 
In this ongoing study, 22 middle-aged female cynomolgus macaques were randomly assigned to receive a western (n = 10) or mediterranean-like diet (n = 12) for 30 months. The monkeys are between 11-13 years of age at the time of tissue collection; this corresponds to 40 to 50-year-old human women. The length of diet is equivalent to about 8 years of intervention in humans. The western diet was designed to mimic the typical American diet: protein and fats from mainly animal sources, high in saturated fat, and high in sodium. The mediterranean diet was designed to mirror a typical diet in the mediterranean region: protein and fats from mainly plant and fish sources, with some dairy proteins, and high in monounsaturated fatty acids. The composition of each diet can be found in Figure 1. Vastus lateralis skeletal muscle tissue is being obtained from each monkey. A small sample of muscle (~20 mg) is placed in BIOPS on ice for fiber separation. Any connective tissue or fat is removed and the bundles are separated gently using needle tip forceps under a dissecting microscope. The separated fibers are transferred to a saponin solution (30 ug/mL saponin in BIOPS) and incubated on ice for 30 minutes. The fibers are then transferred to a wash buffer for 15 minutes on ice. Samples of approximately 2.5 mg (wet weight) are selected and analyzed in the Oroboros O2k using two protocols: SUIT Reference Protocol 2 (RP2) and a protocol adapted from the Neufer Lab at East Carolina University.  The injection strategies and representative traces from preliminary experiments are shown in Figure 2. Analysis will focus on comparing results from both protocols. RP2 is designed to reveal the differences in fatty acid oxidation between the two diet groups and the Neufer protocol will provide detailed information about state 2 and state 3 respiration and respiratory control ratios.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Preparation: Intact cells
Coupling state: OXPHOS Pathway: F, N, S, Gp, CIV, NS, ROX HRR: Oxygraph-2k Event: B2, Oral
- Sticht Center Healthy Aging Alzheimers Prevention, Dept Internal Med, Section Gerontol Geriatrics, Wake Forest School of Medicine, NC, USA. – [email protected]
Figure 1. Composition of diets..
Figure 2. Representative traces from Reference Protocol 2 (A) and Neufer Protocol (B).
References und support
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- Park YMM, Steck SE, Fung TT, Zhang J, Hazlett LJ, Han K, Lee SH, Kwon HS, Merchant AT (2016) Mediterranean diet, dietary approaches to stop hypertension (DASH) style diet, and metabolic health in U.S. adults. Clin Nutr 1-9.
- Perry CGR, Kane DA, Lin CT, Kozy R, Cathey BL, Lark DS, Kane CL, Brophy PM, Gavin TP, Anderson EJ, Neufer PD (2011) Inhibiting myosin-ATPase reveals dynamic range of mitochondrial respiratory control in skeletal muscle. Biochem J 437:215-22.
- Selected mentor: Brian Irving