Removal of Visceral Fat Prevents Insulin Resistance and Glucose Intolerance of Aging
An Adipokine-Mediated Process?
Article Figures & Tables
Figures
- FIG. 1.
Peripheral insulin sensitivity in aging rats. Shown are results for young (2-month-old) and old (20-month-old) F1 hybrids of F344 and Brown Norway rats. The old rats underwent VF removal (VF−), SC fat removal (SC−), or sham operation (SO), or they were calorically restricted (see research design and methods). Glucose uptake (Rd) during hyperinsulinemic (6 mU · kg−1 · min−1) pancreatic clamps is shown. *P < 0.001 vs. SC− and SO rats.
- FIG. 2.
Hepatic insulin sensitivity in aging rats. The ability of insulin to suppress EGP was studied using glucose tracer methodology (see research design and methods). * P < 0.001 vs. SC− and SO rats. Ra, rate of EGP.
- FIG. 3.
Development of diabetes and the regrowth of VF in ZDF rats. At 2 months of age, rats were assigned to either have their epididymal and perirenal fat removed (ZDVF−, n = 12) or undergo a sham operation (ZDVF+, n = 12). Six rats from each group were studied using a pancreatic clamp, and the rest were monitored for 4 months until they developed diabetes. The six ZDVF− rats studied at 4 months had 38% of the fat observed in ZDVF+ rats. When diabetes (defined as glucose >12 mmol/l) appeared, ZDVF− VF accounted for 82% of that observed in ZDVF+ rats. *Percent VF in ZDVF− versus ZDVF+ rats.
- FIG. 4.
Gene expression of TNF-α and leptin. Measurements were performed in epididymal (E), perinephric (R), mesenteric (M), and SC fat after extraction of VF (VF−) or SC fat (SC−). RT and real-time PCR analysis for TNF-α, leptin, and β-actin are described in research design and methods. A: Example of agarose gel analysis of RT-PCR products from different fat depots in SC− and VF− rats. B: Analysis of all real-time PCR data obtained in all rats, corrected for intensity of β-actin and presented in arbitrary units. P < 0.001 vs. mesenteric fat.
- FIG. 5.
Gene expression of resistin (A) and ACRP30 (B). A: Northern blot analysis of brown (B), epididymal (E), perinephric (R), mesenteric (M), and SC fat obtained from SC− rats. B: Real-time PCR data obtained from all rats corrected for the intensity of β-actin and presented in arbitrary units. *P < 0.01 vs. M and SC.
Tables
- TABLE 1
Body composition and fat distribution of aging rats
young SO SC− VF− CR n 6 6 8 6 8 VF/SC removed (g) 0 0 14.9 ± 1.7 15.7 ± 1.3 0 Body weight (g) 291 ± 13 478 ± 19* 451 ± 14* 452 ± 20* 303 ± 9 Lean body mass (g) 264 ± 14 373 ± 14* 364 ± 14* 372 ± 20* 266 ± 8 Non-VF fat mass (g) 21 ± 5 82 ± 10* 65 ± 11* 75 ± 10* 32 ± 6 Total VF after study (g) 5.8 ± 0.9 23.4 ± 4.3* 21.3 ± 1.6* 4.6 ± 0.7† 6.1 ± 1.0 Epididymal (g) 2.9 ± 0.3 9.2 ± 1.6* 8.2 ± 0.7* 0.1 ± 0.1† 2.6 ± 0.5 Perinephric (g) 1.4 ± 0.3 8.3 ± 0.7* 8.1 ± 0.6* 0.4 ± 0.4† 1.9 ± 0.5 Mesenteric (g) 1.5 ± 0.3 5.9 ± 0.4* 4.8 ± 0.6* 4.1 ± 0.4* 1.4 ± 0.4 young (2-month-old), and old (20-month-old) F1 hybrids of F344 and Brown Norway rats were used in these experiments. The old rats underwent VF removal (VF−), SC fat removal (SC−), sham operation (SO), or CR (see research design and methods). The table depicts the amounts of VF or SC removed at the surgery, body weight, lean body mass, non-VF fat mass, total VF, and epididymal, perinephric, and mesenteric fat, which were determined at killing after the experiments.
- *
* P < 0.001 vs. young and CR;
- †
† P < 0.01 vs. young, CR, and SC−. All data are presented as means ± SE.
- TABLE 2
Metabolic characteristics of aging rats
young SO SC− VF− CR n 6 6 8 6 8 Glucose (mmol/l) Basal 7.2 ± 0.2 7.6 ± 0.5 7.4 ± 0.7 7.7 ± 0.3 7.2 ± 0.7 Clamp 7.3 ± 0.3 7.5 ± 0.3 7.5 ± 0.4 7.6 ± 0.3 7.3 ± 0.7 Insulin (μU/ml) Basal 14 ± 2 29.5 ± 3.5* 25 ± 2* 18 ± 2 15 ± 2 Clamp 98 ± 13 96 ± 10 102 ± 11 102 ± 22 92 ± 18 FFA (mmol/l) Basal 0.99 ± 0.15 1.1 ± 0.24 0.81 ± 0.14 1.06 ± 0.14 1.11 ± 0.11 Clamp 0.21 ± 0.08 0.35 ± 0.1 0.23 ± 0.1 0.27 ± 0.04 0.32 ± 0.03 Ra (mg · kg−1 · min−1) Basal 12.1 ± 0.4 9.1 ± 0.3* 8.7 ± 0.2* 10.7 ± 0.3 11.0 ± 0.8 GIR (mg · kg−1 · min−1) Clamp 21.3 ± 3.0 8.4 ± 4.2* 10.4 ± 3.2* 18.0 ± 2.0 21.8 ± 4.6 Gly (mg · kg−1 · min−1) Basal 7.1 ± 0.6 6.0 ± 0.2 6.4 ± 0.5 6.2 ± 0.3 7.4 ± 0.7 Clamp 14.4 ± 1.5 6.9 ± 0.4* 8.6 ± 1.4* 14.7 ± 2.1 13.7 ± 2.0 GS (mg · kg−1 · min−1) Basal 5.0 ± 0.7 3.1 ± 0.1* 2.3 ± 0.5* 4.4 ± 0.3 3.6 ± 0.3 Clamp 12.6 ± 1.4 5.1 ± 0.7* 6.5 ± 0.6* 9.3 ± 0.9 10.4 ± 2.4 Plasma glucose, insulin, FFA concentrations, basal rate of EGP (Ra), glucose infusion rate (GIR), glycolysis (Gly), and glycogen synthesis (GS) during the basal period and during the pancreatic (euglycemic) clamp are shown. These parameters were measured at basal conditions and during the insulin clamps (see group description in research design and methods).
- *
* P < 0.001 vs. young, VF−, and CR. All data are presented as means ± SE.
- TABLE 3
Body composition and fat distribution of ZDF rats
ZDVF+ ZDVF− n 6 8 VF removed (g) 0 10.5 ± 0.3* Body weight (g) 488 ± 17 468 ± 16 Lean body mass (g) 327 ± 19 313 ± 18 Non-VF fat mass (g) 121 ± 15 139 ± 11 Total VF after study(g) 40.0 ± 3.8 15.8 ± 1.1* Epididymal (g) 15.0 ± 2.0 2.0 ± 0.4* Perinephric (g) 15.8 ± 1.7 5.1 ± 0.3* Mesenteric (g) 9.2 ± 0.8 8.8 ± 1.2 At 8 weeks prior to the study, epididymal and perinephric pads were removed in ZDF (fa/fa) rats (ZDVF−), whereas sham operation was performed in control rats (ZDVF+). The table depicts the amounts of VF removed at surgery, body weight, lean body mass, non-VF fat mass, and total VF, epididymal, perinephric, and mesenteric fat that were detected after the study.
- *
* P < 0.001 vs. ZDF+. All data are presented as means ± SE.
- TABLE 4
Metabolic characteristics of ZDF rats
BASAL CLAMP ZDVF+ ZDVF− ZDVF+ ZDVF− n 6 6 6 6 Glucose (mmol/l) 8.9 ± 0.4 8.5 ± 0.5 10.1 ± 0.7* 8.4 ± 0.3 Insulin (pmol/l) 76 ± 9* 44 ± 2 112 ± 10 101 ± 5 FFA (mmol/l) 1.99 ± 0.22 1.67 ± 0.13 2.53 ± 0.11* 1.51 ± 0.16 GIR (mg · kg−1 · min−1) 0 0 0 2.1 ± 0.6 EGP (mg · kg−1 · min−1) 13.8 ± 0.8 13.1 ± 1.6 13.3 ± 0.5* 10.7 ± 0.6† Rd (mg · kg−1 · min−1) 13.8 ± 0.8 13.1 ± 1.6 13.7 ± 0.8 14.2 ± 0.8 Plasma glucose, insulin, FFA levels, glucose infusion rate (GIR), EGP, and glucose uptake (Rd) at basal conditions and during the pancreatic clamps in ZDVF+ (no VF removed) and ZDVF− (VF removed) rats.
- *
* P < 0.001 vs. ZDVF−,
- †
† P < 0.001 vs. basal. All data are presented as means ± SE.
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