The TEMPO Diet Trial: Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity

INTERVENTION: Two 12‐month dietary interventions will be compared: very low energy diet (VLED) and conventional diet. The VLED is an approximately 2,100 kilojoule (500 calorie) per day diet consisting of meal replacement shakes, bars or desserts. No other foods will be consumed during the VLED except for low calorie jelly, strained broth and certain vegetables. The VLED will be used for a minimum of 3 months and a maximum of 5 months, after which time participants will switch to either a partial meal replacement program for further weight loss if required ( 1,500 kcal per day), or the conventional diet for weight maintenance for the remainder of the 12 months. The conventional diet is a lifestyle weight management program consisting of moderate kilojoule restriction ( 500 kcal deficit per day) and involves general recommendations for healthy eating such as increasing fruit and vegetable intake and reducing the intake of processed or fatty foods (e.g. cakes, chocolate, visible fat on meat, etc). CONDITION: Cardiovascular disease Neuroendocrine function Obesity Osteoporosis Sarcopenia PRIMARY OUTCOME: Body weight and composition: ; ; * Body weight / body mass index ; * Fat mass and fat distribution ; * Fat free mass ; * Thigh muscle diameter ; * Bone mass ; ; Methods: Weight will be measured with scales; height (stretch stature) will be measured with a stadiometer for calculation of body mass index; fat mass, fat free mass and bone mass will be determined with the 4‐compartment model for assessment of body composition, comprising independent measures of body density (using the BodPod, Cosmed, Italy), total body water using the deuterium dilution technique, and dual energy X‐ray absorptiometry (DXA, Hologic, Bedford, MA, USA); fat distribution (abdominal obesity) will be estimated from investigation of DXA scans between lumbar vertebrae L2 and L4 and L3 and L6. Additionally, we will use a Siemens Sonata (Malvern, PA, USA) 1.5 Tesla magnet to determine total, visceral and subcutaneous adiposity by magnetic resonance imaging (MRI). MRI will also be used to determine thigh muscle diameter at the midpoint between the patella and inguinal crease. Parameters that affect body composition (adaptive responses to energy restriction): ; ; * Resting metabolic rate ; * Neuroendocrine status (i.e. thyroid hormone function) ; ; Methods: Resting metabolic rate will be measured in the morning in the fasted state with indirect calorimetry using the TrueOne 2400 (Parvo Medics, Sandy, UT, USA) ventilated hood. Thyroid hormone function will be assessed by determining the circulating concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and reverse T3 in morning blood samples collected in the fasted state. Commercial kits or pathology services will be used for these analyses of thyroid function. SECONDARY OUTCOME: Effect of the ketotic state during a very low energy diet on the adaptive responses to energy restriction: ; ; * Appetite ; * Physical activity ; * Resting metabolic rate ; * Neuroendocrine status (e.g. fasting serum concentrations of thyroid hormones, ACTH, cortisol, LH, FSH, estradiol, IGF‐1 etc) ; * Fasting serum gut hormone concentrations ; * Sympathetic reactivity ; * Fasting serum ketone bodies ; ; Methods: Please see Primary outcome 2 and Secondary outcome 4. Other indices of body composition: ; ; * Waist circumference ; * Hip circumference ; * Hepatic fat ; * Thigh fat ; * Muscle strength ; ; ; * Appetite ; * Physical activity ; * Neuroendocrine status (e.g. fasting serum concentrations of ACTH, cortisol, LH, FSH, estradiol, IGF‐1 etc) ; Methods: Waist and hip circumference will be determined using a tape measure. We will use a Siemens Sonata (Malvern, PA, USA) 1.5 Tesla magnet to determine hepatic fat content by magnetic resonance spectroscopy (MRS) as well as magnetic resonance imaging (MRI) to determine thigh fat at the midpoint between the patella and inguinal crease. Muscle strength will be determined using a Jamar hydraulic hand dynamometer (Lafayette Instrument Company, Lafayette, IN, USA). Other parameters that affect body composition (adaptive responses to energy restriction): ; * Fasting serum gut hormone concentrations ; * Circulating or urinary markers of bone turnover ; * Sympathetic reactivity ; * Fasting serum ketone bodies ; ; Methods: Appetite will be assessed using visual analogue scales. Appetite will be measured in the morning after an overnight fast, as well as after a small breakfast meal that participants on the very low energy diet would usually eat as part of their diet. Physical activity will be assessed using Actigraph GT1M accelerometers, worn for 7 days prior to each time point, as well as by a questionnaire on physical activity. Concentrations of hormones, bone turnover markers and ketone bodies will be determined using commercial assay kits or pathology services. Sympathetic reactivity will be assessed by inspiration‐induced vasoconstriction, as determined by laser Doppler fluximetry (MoorVMS‐LDF Laser Doppler Blood Flow Monitor, Moor, England). Parameters of metabolic health: ; ; * Fasting serum glucose ; * Fasting serum insulin ; * Fasting serum triglycerides ; * Fasting serum cholesterol ; * Fasting blood glycosylated hemoglobin ; * Fasting serum C‐reactive protein ; * Blood pressure Vascular function: ; ; * Flow mediated dilatation ; * EndoPAT ; * Carotid intima‐media thickness ; * Pulse wave velocity INCLUSION CRITERIA: * Sedentary (< 60 minutes physical activity / week) * Class I or II obesity (30‐40 kg.m2) * At least 5 years post‐menopausal