Turning the clock forward: New pharmacological and non pharmacological targets for the treatment of obesity.

AIMS: Obesity and its main metabolic complication, type 2 diabetes, have attained the status of a global pandemic; there is need for novel strategies aimed at treating obesity and preventing the development of diabetes. A healthy diet and exercise are basic for treatment of obesity but often not enough. Pharmacotherapy can be helpful in maintaining compliance, ameliorating obesity-related health risks, and improving quality of life. In the last two decades, the knowledge of central and peripheral mechanisms underlying homeostatic and hedonic aspects of food intake has significantly increased. Dysregulation of one or more of these components could lead to obesity. DATA SYNTHESIS: In order to better understand how potential innovative treatment options can affect obesity, homeostatic and reward mechanisms that regulate energy balance has been firstly illustrated. Then, an overview of potential therapeutic targets for obesity, distinguished according to the level of regulation of feeding behavior, has been provided. Moreover, several non-drug therapies have been recently tested in obesity, such as non-invasive neurostimulation: Transcranial Magnetic Stimulation or Transcranial Direct Current Stimulation. All of them are promising for obesity treatment and are almost devoid of side effects, constituting a potential resource for the prevention of metabolic diseases. CONCLUSIONS: The plethora of current anti-obesity therapies creates the unique challenge for physicians to customize the intervention, according to the specific obesity characteristics and the intervention side effect profiles; moreover, it allows multimodal approaches addressed to treat obesity and metabolic adaptation with complementary mechanisms.

Deep transcranial magnetic stimulation in combination with skin thermography in obesity: a window on sympathetic nervous system.

AIMS: Obesity is known to be associated with an altered thermoregulation as well as a dysregulation of sympathetic nervous system (SNS). Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the SNS, we hypothesized a potential role of dTMS in affecting thermoregulation in obesity. Aims of the study were to monitor the effect of a single session of dTMS on body temperature in subjects with obesity, and to correlate the dTMS-induced changes in body temperature with activation of the SNS (epinephrine and norepinephrine release). METHODS: Twenty-nine subjects with obesity [5 M, 24 F; age 50 (IQR: 58, 38) yrs; BMI 36.1 (IQR: 33.9, 38.7) kg/m2] were randomized into 2 groups receiving a single session of high frequency stimulation (HF) or sham stimulation. Under neutral thermal conditions, infrared thermography was utilized to assess bilateral fingernail-beds and abdominal temperature. RESULTS: During a single session HF, the average temperature of both fingernail-beds decreased. Right-hand temperature difference was statistically greater in HF vs Sham: median = - 1.45 (IQR: - 2.0, - 1.0)  °C for HF, p = 0.009. While temperature variation in the fingernail-bed of left hand was not statistically significant in HF compared to Sham: median = - 1.26 (IQR: - 1.6, -0.5) °C, p = 0.064. Concurrently, when estimating the effect of norepinephrine variation on temperature change of fingernail-bed of left hand, a borderline significant positive association was estimated (beta = 1.09, p = 0.067) in HF. CONCLUSIONS: Deep TMS revealed to be effective in modulating temperature in subjects with obesity, partially reversing obesity-induced alterations in heat production and dissipation with a potential SNS-mediated mechanism.