Immunometabolic Effects of Non-drug Strategies in the Clinical Management of Obesity: Translational Study
Condition: Obesity; Obesity, Abdominal; Obesity, Visceral; Female
MeSH terms: Obesity; Obesity, Abdominal
Study type: Interventional

Summary: 
      Forty women aged between 18 and 75 years-old with a BMI> 30kg/m2 are recruited to participate
      in the evaluation of their medical management. They participate in an 8-week protocol as part
      of hospital medical treatment for weight loss at the Oxford Polyclinic in Cannes (IPOCA). The
      effects of 2 independent variables will be studied: (1) an adapted physical activity program
      and (2) nutritional supplementation with R-α-Lipoic acid (2x300mg/d) versus placebo
      (double-blind). The volunteers are randomly assigned to the different groups: Placebo with or
      without exercise groups and ALA with or without exercise groups. At the start of the protocol
      (T0), at 4 weeks (T4) and at 8 weeks (T8), various measurements are carried out (physical
      capacities, nutritional status, body composition, distribution of adipose mass by CT-scan). A
      venous sample taken for all participants is done at T0, T4 and T8 to investigate the immune
      profile of circulating T lymphocytes.

      This project is part of a translational research project to assess current care and to
      investigate the immunometabolic effects of a non-drug medical care of obesity (adapted
      physical activities, nutritional supplementation with α-lipoic acid, quality of food intake).
    

Detailed description: 
      Obesity-related inflammation is central to the development of type 2 diabetes and potentiated
      by advancing age, inactive behavior and sedentary lifestyle. Metabolism and immunity are
      entangled in their respective effects: the pathways of inflammation are involved in
      metabolism and the metabolic state plays a predominant role in immune function. Physical
      activity and calorie restriction are first-line, non-drug strategies recommended in reducing
      obesity and insulin resistance and then prevent type 2 diabetes. However, the impact of their
      combined effects on circulating immune cells or those residing in adipose tissue and skeletal
      muscle, remains insufficiently understood to allow a nutritional prescription (i.e., quality
      of nutritional intake and efficient doses of physical activity) favorable to preventive
      medical care, individualized, and effective. If the risk associated with an increase in
      visceral fat mass is linked to a change in the pro/anti-inflammatory status, it is essential
      to reduce this risk by acting on its cause, regardless of the weight loss. In a context of
      low-grade inflammation, these effects could lead to an anti-inflammatory profile of T cells,
      specifically regulatory T cells (Treg) whose metabolism is extremely "flexible" at the
      periphery and into visceral adipose tissue (directly involved in inflammation of obesity).

      ALA (Alpha-Lipoic Acid) is known to play a pivotal role in cellular redox status and energy
      metabolism by modulating inflammatory and metabolic signaling pathways such as those of
      NF-kB, JNK, PI3K/Akt, p38 MAPK, AMPK or PPARβ/δ. As ALA is a possible metabolic modulator, it
      would affect the metabolism of T cells. And therefore ALA could be a complementary measure to
      non-drug strategies by potentiating the correction of the inflammatory state linked to
      obesity.
    

Intervention name(s): Alpha lipoic acid (plus full hospitalization); Placebo (full hospitalization: dietary monitoring with an adapted physical activity program)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Women are included in an 8-weeks randomized double-blind against placebo supplementation study with ALA (eight per group) according to the following criteria:
Inclusion criteria: BMI> 30; aged between 18 and 75 years. Non-inclusion criteria: HLA-DRB1*04-03/06 polymorphisms; recent hospitalization (<1 month); food supplement based on antioxidant; medicated in fibrate / telmisartan (modulator of PPARs); patients presenting an acute inflammatory state.
Exclusion criteria: Pregnant and/or lactating women; not affiliated with social security; not mutual health insurance; person deprived of liberty; participation in clinical research in the last 6 months.
Patients included in this clinical trial benefited from a complete hospitalization including dietary monitoring with a personalized food plan and an adapted physical activity program. α-LA (2x300mg/day of R-ALA) was administered double-blinded in the form of 2 capsules apart from meals.; Women are included in an 8-weeks randomized in placebo group. Patients included in this clinical trial benefited from a complete hospitalization including dietary monitoring with a personalized food plan and an adapted physical activity program. Placebo (2x300mg/day) was administered double-blinded in the form of 2 capsules apart from meals.
Intervention MeSH terms: Thioctic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Regulatory T cells; Immunometabolic; Alpha lipoic acid; Physical activity; Non-drug strategy; Obesity