Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans

Abstract

1. The effect of intraneural electrical stimulation of the lateral femoral cutaneous nerve on lipolysis in the innervation territory of the stimulated nerve fascicle was studied in seven healthy women. Lipolysis was evaluated by microdialytic measurement of the interstitial glycerol concentration in subcutaneous adipose tissue. 2. Ten minutes of unilateral intraneural stimulation elicited a 22 +/- 8 % (mean +/- s.e.m.) increase in glycerol levels in the stimulated region (P < 0.05), whereas no change was registered in the corresponding area of the contralateral unstimulated leg. 3. Significantly higher glycerol levels in the stimulated vs. contralateral unstimulated region (47 +/- 13 %, P < 0.05) were already observed at baseline (30 min resting period preceding the 10 min stimulation), in all probability as a consequence of the nerve searching procedure and trial stimulations. After the 10 min stimulation, the overall glycerol increase was 72 +/- 17 % compared with the contralateral leg, illustrating the degree of lipolysis induced by the whole experimental procedure. 4. The sympathetic discharge in the lateral femoral nerve (6 recordings) showed typical characteristics of skin sympathetic activity, and the firing pattern was strikingly similar to simultaneously recorded sympathetic discharge in cutaneous nerve fascicles innervating regions without prominent subcutaneous fat stores (2 double nerve recordings). Thus, no component of cutaneous sympathetic outflow specific for the nerve innervating prominent subcutaneous fat stores could be identified. 5. Our findings suggest that sympathetic nerve fibres travelling in cutaneous nerve fascicles exert a regulatory influence on subcutaneous fat tissue in humans. The combination of intraneural recording/stimulation and subcutaneous microdialysis provides a model for evaluating neural control of human fat metabolism.

Figure 1. Schematic drawing of the experimental setup

After a suitable stimulation/recording site within the lateral cutaneous femoral nerve (N cut fem lat) was established, 2 microdialysis probes were inserted in the receptive field of the impaled nerve fascicle and one additional control probe in a corresponding area of the contralateral leg. Microdialysis probes were perfused at a constant rate of 2.5 μl min⁻¹. Ref electr, reference electrode; LD, laser Doppler.

Figure 2. Interstitial glycerol concentrations in the stimulated subcutaneous area and the unstimulated control area in the contralateral leg in 7 healthy female subjects

Glycerol concentrations were significantly higher in the stimulated subcutaneous area (○) from the start of measurement, in all probability due to the preceding neural search procedure and trial stimulations, and was further increased during 10 min of intraneural stimulation while no effect was seen in the control area of the contralateral leg (•). * P < 0.05.

Figure 3. Double nerve recordings

Excerpts from simultaneous recordings of sympathetic nerve activity in the lateral cutaneous femoral nerve (n cut fem) and a cutaneous fascicle of the peroneal nerve (n per) (subject A, A), and in the lateral cutaneous femoral nerve and a cutaneous fascicle of the median nerve (n med) (subject B, B). No specific lipomotor activity could be discerned within the mean voltage neurogram of the lateral cutaneous femoral nerve, when compared with the firing pattern in fascicles innervating territories without prominent subcutaneous fat stores.

Figure 4. Power spectra of resting sympathetic nerve activity in the two double nerve recordings in Fig. 3, as well as respiration and ECG

Note that the two nerve pairs show similar spectral peaks corresponding to the respiratory frequency peak (at 0.2 Hz), whereas neither of the nerves show a significant peak related to heart rate (at 1 Hz). Arbitrary units on y-axis.