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)

Overweight and obesity are major public health challenges worldwide, and their prevalenceincreases with age, partly because of age‐related metabolic and hormonal changes. Beyondtotal fat mass, abdominal and particularly visceral fat accumulation is stronglyassociated with chronic low‐grade inflammation, insulin resistance, hypertension andcardiovascular disease. Men are more likely to display an android fat distribution, whilepremenopausal women generally show a more protective gynoid distribution. However,declining sex hormone concentrations after menopause promote abdominal and visceral fataccumulation, increasing cardiometabolic risk.Physical activity is a cornerstone of overweight and obesity management. High‐intensityinterval training (HIIT) is an effective strategy for reducing total, abdominal andvisceral fat and may produce greater benefits than moderate‐intensity continuoustraining. Since 2016, our team has conducted several studies and reviews showing thatHIIT performed on a cycle ergometer or treadmill, alone or combined with resistancetraining, 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 enhancecardiovascular, respiratory, circulatory, haematological and skeletal muscle adaptations.The Live Low‐Train High model allows participants to live under normoxic conditions whilebeing exposed to hypoxia only during exercise. Hypoxic HIIT has proved feasible and safein people with metabolic disorders or physical deconditioning, including at simulatedaltitudes of 4,000‐5,000 m. However, only two studies have suggested that hypoxic HIITmay enhance fat mass loss in people with overweight or obesity. Neither specificallyassessed abdominal or visceral fat, and neither focused on postmenopausal women.Several mechanisms may contribute to HIIT‐induced fat loss, including increasedcatecholaminergic stimulation and lipid oxidation during recovery, excess post‐exerciseoxygen consumption and changes in appetite regulation. The gut microbiota may alsocontribute to the regulation of adipose tissue and cardiometabolic health. Physicalactivity can increase bacterial diversity and promote beneficial taxa, particularlyshort‐chain fatty acid‐producing bacteria. Our previous HIIT studies identifiedassociations between changes in selected bacteria and reductions in total or abdominalfat mass. Hypoxic exposure may also alter gut microbiota composition and abundance, witheffects depending on the severity and type of hypoxia.This study will assess the effects of a 3‐month cycle‐ergometer HIIT programme, performedthree times per week under hypoxic versus normoxic conditions, in adults aged 50‐75 yearswith overweight or obesity. The primary objective is to determine whether hypoxic HIITproduces a greater reduction in abdominal and visceral fat mass than the same trainingperformed 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, ApoA1and the ApoB/ApoA1 ratio; high‐sensitivity C‐reactive protein and fibrinogen; systolicand diastolic blood pressure; blood biophysical properties; and faecal microbiotarichness, diversity and taxonomic composition. Lipid oxidation during prolongedmoderate‐intensity exercise, maximal oxygen uptake and maximal aerobic power will also beassessed 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 comparedwith normoxic training. We further hypothesise that hypoxia will modify faecal microbiotacomposition and that changes in selected bacterial taxa will be associated with changesin body composition and cardiovascular risk markers.The ultimate aim is to improve the management of adults aged 50‐75 years with overweightor obesity by developing an effective 3‐month HIIT programme performed under controlledhypoxic conditions.