Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis

Abstract

Background: Adipocyte numbers and peroxisome proliferators activated receptorγ (PPARγ) expression of retroperitoneal tissue increased while area under the curve (AUC) during the glucose tolerance test (GTT) was reduced in rats subjected to certain feed withdrawal (FW) regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h) or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age) FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control).

Methods: Growth, body composition, adipocyte numbers, PPARγ expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM) and subcutaneous (SQ) fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum.

Results: Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively) in pigs in FW treatments. In OM fat; cell numbers, glucose Universal14C [U14C] incorporation into fat and rate of incorporation per 104 cells was greatest for cells with diameters of 90-119 μm. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191%) number of adipocytes, increased (p = 0.0234) glucose U14C incorporation into adipocytes and greater (p = 0.0872) rate of glucose uptake into cells of 119-150 μm diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 μm diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively) than for those in FWx4 treatment, yet PPARγ expression and total cell number were not affected by treatment.

Conclusions: Results suggest that FW regimens influence fat cell function or lipogenesis rather than number, affecting glucose metabolism and may have implications in drug-free control of metabolic syndrome symptoms.

Figure 1

Schematic for application of feed withdrawal (FW) treatments.

Figure 2

Blood glucose concentration curves during the glucose tolerance test of castrated pigs at 21 wk of age undergoing control (no feed withdrawal), single feed withdrawal (FWx1) for 48 h at 19 wk or multiple feed withdrawal (FWx4), FW for 24 h at age 7 and 11 wk and for 48 h FW at 15 and 19 wk. Trends (p = .1048 and .0968) towards decreased glucose concentrations were observed for fasting and 120 min post glucose consumption samples respectively from pigs in the FW treatments relative to values for pigs in the control treatment (n = 3).

Figure 3

Plasma insulin concentration curves during the glucose tolerance test of castrated pigs at 21 wk of age undergoing control (no feed withdrawal), single feed withdrawal (FWx1) for 48 h at 19 wk or multiple feed withdrawal (FWx4) for 24 h at age 7 and 11 wk and for 48 h at 15 and 19 wk. (n = 3)

Figure 4

Glucose Universal ¹⁴C uptake by cells of different diameter (μm) and from omental adipose tissue of pigs in the feed withdrawal (FW) treatments: control (no feed withdrawal), single FW (FWx1) for 48 h at 19 wk or multiple FW (FWx4) for 24 h at age 7 and 11 wk and for 48 h at 15 and 19 wk. a. cells per/mg of fat sample, b. counts/min/mg of fat and c. counts/min/10⁴ cells. Cell numbers and U¹⁴C glucose incorporation rate for cells in the diameter range of 119-150 μm tended (p = .0685 and .0872, respectively) to be greater for pigs in the FWx4 treatment relative to the other treatments, while counts per minute of fat/mg of sample was greater (p = .0234) for the same cells. (n = 5, 6 and 7 for control, FWx1, and FWx4 respectively)

Figure 5

Glucose Universal ¹⁴C uptake by cells of different diameter (μm) and from subcutaneous adipose tissue of pigs in the feed withdrawal (FW) treatments: control (no feed withdrawal), single FW (FWx1) for 48 h at 19 wk or multiple FW (FWx4) for 24 h at age 7 and 11 wk and for 48 h at 15 and 19 wk. a. cells per/mg of fat sample, b. counts/min/mg of fat and c. counts/min/10⁴ cells. Cell numbers in the diameter ranges of 22-60 and 60-90 μm tended (p = .0773, .0613 respectively) to be greater for pigs in the FWx1 relative to those in the FWx4 treatment. (n = 7, 6 and 7 for control, FWx1, and FWx4 respectively)