Project: Neuroinflammation and dysregulation of eating behavior
About
The projects developed in this second research axis are at the interface between neuroimmunoendocrinology, nutrition and metabolism.
The chemokine CCL5, a key regulator of neuroinflammation and type 2 diabetes associated with nutritional obesity.
Keywords: Chemokines, Neuroinflammation and Energy Balance
| Type 2 diabetes (T2D) is the most common form of diabetes, accounting for more than 90% of adult diabetes cases. In France, T2D affects nearly 5% of the population. T2D is a metabolic disease characterized by chronic hyperglycemia induced by impaired insulin secretion and insulin resistance. These T2D markers may result from a chronic pro-inflammatory state of adipose tissue, associated with secretion of diabetogenic cytokines (IL-1beta, IL-6, TNF-alpha) and chemokines (RANTES/CCL5, MCP1/CCL2). Adipose tissue would thus lose its ability to store fats and sugars, which would accumulate ectopically in the organs. All of these mechanisms would cause insulin resistance. Secreted pro-inflammatory cytokines and chemokines would be the promoters of systemic and nerve center inflammation, responsible for metabolic syndrome and T2D. |  |
| Chemokine CCL5 |
The Western lifestyle promotes the development of T2D and obesity. The link between obesity and metabolic complications such as T2D is well established at the epidemiological level. Indeed, nearly 3 times more overweight people than those of normal weight report diabetes and 7 times more in case of obesity. Conversely, 43% of type 2 diabetics are obese (ObEpi Roche 2012). The increase in body mass index (BMI) is a major risk factor for associated chronic pathologies such as cardiovascular diseases, dyslipidemia and T2D. However, the link between T2D and obesity remains poorly defined at the etiological level.
Our working hypothesis is that The chemokine CCL5 regulates the activity of HT neurons involved in the control of feeding behavior and carbohydrate homeostasis.
CCL5 would be an important initiating factor in the development of T2D associated with nutritional obesity. We study the early role of the chemokine CCL5 in the control of energy balance, obesity, T2DM anddiabetic peripheral neuropathy which is one of the most common diabetic complications, affecting up to half of patients with T2DM.
Main previous works
2016…
This work, established in the context of unprovoked involuntary weight loss, associated with a
deterioration of health status, identify CCL2 and other inflammatory proteins as
regulators of energy balance and eating behavior. These are all targets
promising molecular mechanisms for establishing new therapies in the context of non-dieting-related weight loss or anorexia nervosa.
Le Thuc O et al. (2016) EMBO Rep. 17:1738-1752.
2020…
Our work shows that short-term exposure to dietary fat exacerbates inflammation
postprandial hypothalamic and modulates the gene expression of hypothalamic neuropeptides that
regulate energy balance. Both of these responses involve GFAP-positive cells and
microglial cells. Thus, recurrent and exacerbated postprandial inflammation in the brain could
promote obesity and must be characterized to address this global crisis.
Cansell C et al. (2020) Glia 69:42–60.
The work presented was supported by the French National Research Agency (ANR) as part of the 2021 generic call for projects (MicroFlamEAT project), focusing on the role of the postprandial microglial inflammatory response in the cerebral control of appetite, with €90,000 in funding awarded to the team as a partner.
In addition, a grant of €15,000 was obtained in 2021 from the French-Speaking Diabetes Society, in partnership with Roche Diabetes Care, as part of a project coordinated by the team.
