Hypothesis paper: electroacupuncture targeting the gut–brain axis to modulate neurocognitive determinants of eating behavior—toward a proof of concept in the obese minipig model

Abstract

Acupuncture has thousands of years of history and perspective for the treatment of many health problems and disorders. Beneficial effects of acupuncture on obesity have been demonstrated at various levels in animals and clinical trials, with almost no adverse effect, even when combined with local electrical stimulation, i.e., electroacupuncture (EA), a way to potentiate the effects of acupuncture. However, there is still scattered evidence about the impact of EA on brain functions related to the control of eating behavior, and notably on the gut-brain axis mechanisms involved in these putative central modulations. During the past 10 years, we have described a convincing diet-induced obese minipig model, and successfully implemented brain imaging and neurocognitive approaches to challenge mechanistic hypotheses and innovative therapeutic strategies. In the present article, we propose to confront the current literature on the acupuncture and EA effects on the gut-brain axis and obesity with the latest developments in nutrition and neuroscience research using the minipig model. Our aims are to (a) elaborate functional hypotheses on the gut-brain mechanisms underlying EA effects on obesity, and especially on the role of the vagus nerve, and (b) present the rational for testing these hypotheses in the minipig model.

Acute Effects of Different Electroacupuncture Point Combinations to Modulate the Gut-Brain Axis in the Minipig Model

“…This study is the first to implement electroacupuncture (EA) in the minipig model with the aim of modulating gut-brain signals and the BOLD fMRI hemodynamic responses in brain regions involved in food intake control, pleasure, and motivation. In a previously published hypothesis paper [ 1 ], we identified three acupoint combinations likely to have an effect on the gut-brain axis, including changes in the autonomic nervous system and especially the sympathovagal balance, as well as of hunger and satiety plasma markers. The present princeps study demonstrated that acute EA on specific acupoints significantly modulated several of these physiological and metabolic parameters compared to basal, sham, and/or control stimulation, with contrasting effects in terms of BOLD responses in brain regions involved in the hedonic and cognitive control of food intake.…”

“…Traditional acupuncture and one of its modern derivatives, electroacupuncture (EA), are increasingly used for treating various diseases and especially gastrointestinal disorders [ 1 , 2 ]. Acupuncture and EA are usually appreciated for their limited adverse effects and good clinical outcomes.…”

“…Single acupuncture points were often used in rodent experiments, but in clinical practice, a combination of different acupoints is usually recommended, and in Chinese medicine theory, point combinations provide better results than single-point stimulation thanks to synergetic effects. In our study, we chose three different acupoint combinations and a sham-point combination, as initially described in a previously published hypothesis paper [ 1 ]: a head-abdomen point combination associating Dafengmen (#70) and Sanwan (#35), a back point combination associating Liumai (#27) and Pishu (#28), and a leg point combination associating bilateral Housanli (#63) and Hangou (#79). The precise location of these pig acupoints and their correspondence with human acupoints will be described later.…”

“…Our aim in this study was to compare, in a large animal model close to the human, different EA combinations by assessing their immediate effects on different parameters that are important for food intake control. In the hypothesis paper [ 1 ], we published preliminary to the preclinical trial presented here we identified several key markers relevant to investigate the gut-brain axis and food-brain cognition. Our hypothesis is that the EA combinations chosen for this preclinical trial will modulate differently from sham treatment the plasma level of gut hormones, glucose metabolism, autonomic nerve balance, and most importantly the brain responses concomitant to acute EA.…”

Obesity Animal Models for Acupuncture and Related Therapy Research Studies

“…Surprisingly, we found no study aimed at investigating the effects of acupuncture or EA in a pig model of obesity or hyperphagia (an abnormally strong sensation of hunger or desire to eat often leading to or accompanied by overeating) nor in any other large animal model, which highlights the complete lack or research in this promising field. We recently published a hypothesis study [ 178 ] presenting the rationale and a methodological approach to investigate the effects of electroacupuncture in obese minipigs. This ongoing study is the first of its kind.…”