High-Intensity Interval Training in Low Versus Normal Oxygen: Effects on Body Fat and Gut Health in Adults Aged 50-75 With Overweight or Obesity (HYPOXFAT) (HYPOXFAT)

Overweight and obesity are major public health challenges worldwide, and their prevalence increases with age, partly because of age-related metabolic and hormonal changes. Beyond total fat mass, abdominal and particularly visceral fat accumulation is strongly associated with chronic low-grade inflammation, insulin resistance, hypertension and cardiovascular disease. Men are more likely to display an android fat distribution, while premenopausal women generally show a more protective gynoid distribution. However, declining sex hormone concentrations after menopause promote abdominal and visceral fat accumulation, increasing cardiometabolic risk.

Physical activity is a cornerstone of overweight and obesity management. High-intensity interval training (HIIT) is an effective strategy for reducing total, abdominal and visceral fat and may produce greater benefits than moderate-intensity continuous training. Since 2016, our team has conducted several studies and reviews showing that HIIT performed on a cycle ergometer or treadmill, alone or combined with resistance training, reduces total and abdominal fat mass in people with overweight or obesity, regardless of age, sex or hormonal status.

HIIT can also be performed under real or simulated hypoxic conditions to enhance cardiovascular, respiratory, circulatory, haematological and skeletal muscle adaptations. The Live Low-Train High model allows participants to live under normoxic conditions while being exposed to hypoxia only during exercise. Hypoxic HIIT has proved feasible and safe in people with metabolic disorders or physical deconditioning, including at simulated altitudes of 4,000-5,000 m. However, only two studies have suggested that hypoxic HIIT may enhance fat mass loss in people with overweight or obesity. Neither specifically assessed abdominal or visceral fat, and neither focused on postmenopausal women.

Several mechanisms may contribute to HIIT-induced fat loss, including increased catecholaminergic stimulation and lipid oxidation during recovery, excess post-exercise oxygen consumption and changes in appetite regulation. The gut microbiota may also contribute to the regulation of adipose tissue and cardiometabolic health. Physical activity can increase bacterial diversity and promote beneficial taxa, particularly short-chain fatty acid-producing bacteria. Our previous HIIT studies identified associations between changes in selected bacteria and reductions in total or abdominal fat mass. Hypoxic exposure may also alter gut microbiota composition and abundance, with effects depending on the severity and type of hypoxia.

This study will assess the effects of a 3-month cycle-ergometer HIIT programme, performed three times per week under hypoxic versus normoxic conditions, in adults aged 50-75 years with overweight or obesity. The primary objective is to determine whether hypoxic HIIT produces a greater reduction in abdominal and visceral fat mass than the same training performed in normoxia.

Secondary outcomes will include total and regional fat and lean mass; fasting glucose, insulin, HbA1c and HOMA-IR; total cholesterol, triglycerides, HDL-C, LDL-C, ApoB, ApoA1 and the ApoB/ApoA1 ratio; high-sensitivity C-reactive protein and fibrinogen; systolic and diastolic blood pressure; blood biophysical properties; and faecal microbiota richness, diversity and taxonomic composition. Lipid oxidation during prolonged moderate-intensity exercise, maximal oxygen uptake and maximal aerobic power will also be assessed before and after the intervention.

We hypothesise that hypoxic training will enhance improvements in body composition, metabolic and cardiovascular risk factors, aerobic fitness and lipid oxidation compared with normoxic training. We further hypothesise that hypoxia will modify faecal microbiota composition and that changes in selected bacterial taxa will be associated with changes in body composition and cardiovascular risk markers.

The ultimate aim is to improve the management of adults aged 50-75 years with overweight or obesity by developing an effective 3-month HIIT programme performed under controlled hypoxic conditions.