The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance.

OBJECTIVE: To demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it. METHODS: Rats were raised with high-fat diets for 8 weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic-euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16 m/min and 50 min, and speed increased 1m/min and duration time increased 5 min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured. RESULTS: Rats fed with high-fat diets for 8 weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P<0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P<0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P<0.05) following the development of insulin resistance, and it increased (P<0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P>0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P<0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P<0.05) following the development of insulin resistance, and it decreased (P<0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P>0.05). CONCLUSIONS: In conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues.

3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-ethoxy)ethylidene]-ß-D-mannopyranose 0.11-hydrate.

The title compound, C(16)H(24)O(10)·0.11H(2)O, is a key intermediate in the synthesis of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), which is the most widely used molecular-imaging probe for positron emission tomography (PET). The crystal structure has two independent molecules (A and B) in the asymmetric unit, with closely comparable geometries. The pyranose ring adopts a (4)C(1) conformation [Cremer-Pople puckering parameters: Q = 0.553 (2) Å, θ = 16.2 (2)° and φ = 290.4 (8)° for molecule A, and Q = 0.529 (2) Å, θ =15.3 (3)° and φ = 268.2 (9)° for molecule B], and the dioxolane ring adopts an envelope conformation. The chiral centre in the dioxolane ring, introduced during the synthesis of the compound, has an R configuration, with the ethoxy group exo to the mannopyranose ring. The asymmetric unit also contains one water molecule with a refined site-occupancy factor of 0.222 (8), which bridges between molecules A and B via O-H···O hydrogen bonds.

Ethyl 4-chloro-3,5-dinitro-benzoate.

In the title compound, C(9)H(7)ClN(2)O(6), the nitro groups and the ester group make dihedral angles of 44.0 (1), 89.6 (1) and 164.1 (1)°, respectively, with the benzene ring. In the crystal, mol-ecules are linked through weak C-H⋯O hydrogen-bonding inter-actions. Mol-ecules are stacked via π-π inter-actions about inversion centers, with a centroid-centroid distance of 3.671 (2) Å.

Isopropyl 4-nitro-benzoate.

In the mol-ecule of the title compound, C(10)H(11)NO(4), the nitro group is approximately coplanar with the benzene ring [dihedral angle = 4.57 (10)°], while the carboxyl-ate group is slightly twisted, making an angle of 12.16 (8)°. In the crystal, weak inter-molecular C-H⋯O hydrogen bonding and π-π stacking inter-actions [centroid-centroid distances = 3.670 (2) and 3.665 (2) Å] are observed.

2,3,5-Trimethyl-1,4-hydro-quinone.

The mol-ecule of the title compound, C(9)H(12)O(2), is approximately planar (mean atomic deviation = 0.0346 Å) and disposed about a crystallographic centre of symmetry. The H atom of the benzene ring is disordered over four orientations, with occupancies of 0.100 (3) and 0.401 (3) at the C atoms in the 2- and 3-positions and the same at their symmetric location. The H atoms of methyl group at the 2-position are disordered over two positions of equal occupancy. In the crystal structure, adjacent mol-ecules are linked through O-H⋯O hydrogen bonds, forming a two-dimensional network.

Dimethyl 5-amino-2,4,6-triiodo-isophthalate.

The title compound, C(10)H(8)I(3)NO(4), crystallizes with two mol-ecules in the asymmetric unit. The I atoms and the benzene ring plane in the two mol-ecules are approximately coplanar, the I atoms deviating by -0.1631 (1), 0.0704 (1) and -0.0507 (1) Šfrom the mean plane of the benzene ring in one mol-ecule and by 0.1500 (1), -0.0034 (1) and -0.1213 (1) Šin the other. The planes of the ester groups are almost orthogonal to those of the benzene rings in both mol-ecules, forming dihedral angles of 83.5 (3), 76.4 (3), 97.3 (1) and 75.7 (1)°. The mean planes of the benzene rings in two mol-ecules are inclined at 69.8 (3)° with respect to each other. In the crystal, inter-molecular I⋯O inter-actions link the mol-ecules into infinite chains. In addition, N-H⋯O and non-classical C-H⋯O hydrogen bonds are observed.

Ethyl 2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetate.

In the title compound, C(8)H(11)N(3)O(4), the dihedral angle between the imidazole ring and the ethyl acetate plane is 103.1 (8)°. The crystal packing is stabilized by weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds.

Glycine ethyl ester hydro-chloride.

In the crystal structure of the title compound, C(4)H(10)NO(2) (+)·Cl(-) (systematic name: 3-eth-oxy-3-oxopropan-1-aminium chlor-ide), there are strong inter-molecular N-H⋯Cl, C-H⋯Cl and C-H⋯O hydrogen-bonding inter-actions between the free chloride anion and the organic cation, resulting in a two-dimensional supra-molecular network in the ab plane.

2-Chloro-ethyl 4-nitro-benzoate.

The title compound, C(9)H(8)ClNO(4), crystallizes with two mol-ecules in the asymmetric unit. In each mol-ecule, the carboxyl-ate group is nearly coplanar with the benzene ring, forming dihedral angles of 2.4 (1) and 4.9 (1)°. In the crystal, mol-ecules are linked through weak C-H⋯O and C-H⋯Cl hydrogen bonds. A short O⋯N contact of 2.7660 (19) Šoccurs between the nitro groups of adjacent mol-ecules.

3,5-Dinitro-benzoyl chloride.

The carbonyl chloride group in the title compound, C(7)H(3)ClN(2)O(5), is disordered over two orientations with occupancies of 0.505 (5) and 0.495 (5). The mol-ecule is approximately planar, the dihedral angle between the carbonyl chloride plane and benzene ring being 9.6 (4)° in the major disorder component and 7.1 (4)° in the minor component. The nitro group at the 5-position is twisted, forming a dihedral angle of 6.7 (4)°. The crystal packing is stabilized by C-H⋯O hydrogen bonds.

2-(Carbazol-9-yl)acetic acid.

In the title compound, C(14)H(11)NO(2), the tricyclic aromatic ring system is essentially planar [maximum deviation = 0.025 (2) Å]. The dihedral angle between the two benzene rings is 2.8 (5)°, while the carboxyl group forms a dihedral angle of 88.5 (1)° with the pyrrole ring. Inter-molecular O-H⋯O hydrogen bonds may contribute to the overall stabilization of the crystal structure.

Methyl 4-nitro-benzoate.

In the mol-ecule of the title compound, C(8)H(7)NO(4), the nitro group is approximately coplanar with the benzene ring [dihedral angle = 0.6 (1)°], while the dihedral angle between the methoxy-carbonyl group and the benzene ring is 8.8 (1)°. In the crystal structure, weak inter-molecular aromatic C-H⋯O(carbox-yl) and C-H⋯O(nitro) hydrogen-bonding inter-actions are present.

5,6,7,8-Tetra-hydro-naphthalene-1-carboxylic acid.

In the mol-ecule of the title compound, C(11)H(12)O(2), the cyclo-hexane ring adopts a half-chair conformation. In the crystal structure, mol-ecules are linked into centrosymmetric dimers by pairs of O-H⋯O hydrogen bonds, and the dimers are linked together by π-π inter-actions [centroid-centroid distance = 3.8310 (13) Å] and C-H⋯O bonds.

Diethyl 5-amino-2,4,6-triiodo-isophthalate.

The title compound, C(12)H(12)I(3)NO(4), crystallizes with two mol-ecules in an asymmetric unit. In one of the mol-ecules, the conformation of the O-C-O-C in one ester group is cis and trans in the other. The corresponding conformations for both the ester groups in the other mol-ecule are trans. The I atoms and the benzene rings in the two mol-ecules are approximately coplanar, the I atoms deviating by 0.219 (14), 0.056 (15) and -0.143 (14) Šfrom the mean plane of the benzene ring in one mol-ecule and 0.189 (14), -0.162 (15) and -0.068 (14) Šin the other. The planes of the ester groups are almost orthogonal to those of the benzene rings in both mol-ecules, forming dihedral angles of 88.1 (4), 72.2 (4), 73.0 (4) and 86.6 (4)°. The mean planes of the benzene rings in the two mol-ecules are inclined at 74.6 (4)° with respect to each other. In the crystal, inter-molecular I⋯O inter-actions [3.138 (7) and 3.144 (7) Å] link the mol-ecules into infinite chains along the a axis. In addition, non-classical C-H⋯O hydrogen bonds are observed.

4,7-Diphenyl-2,9-bis-(trichloro-meth-yl)-1,10-phenanthroline.

In the title compound, C(26)H(14)Cl(6)N(2), the phenanthroline ring system is essentially planar, with an r.m.s. deviation of 0.048 (6) Å, and makes dihedral angles of 64.8 (14) and 66.6 (6)° with the two terminal phenyl rings. One of the trichloro-methyl groups is disordered over two positions, with occupancies of 0.42 (2) and 0.58 (2).

Methyl 4-chloro-3,5-dinitro-benzoate.

In the mol-ecule of the title compound, C(8)H(5)ClN(2)O(6), the two nitro groups and the ester group make dihedral angles of 29.6 (1)°, 82.3 (1)° and 13.7 (1)°, respectively, with the benzene ring. In the crystal structure weak C-H⋯O inter-actions are present.

Methyl 3-carboxy-5-nitrobenzoate.

The structure of the title compound, C(9)H(7)NO(6), is essentially planar [maximum deviation 0.284 (2)Å] except for the methyl H atoms. The crystal structure is stabilized by asymmetric O-H⋯O hydrogen bonds linking the hydrogen carboxyl-ates into pairs around the inversion centres. There is also π-π stacking of the benzene rings [centroid-centroid distance 3.6912 (12) Å].

2-Isopropoxyphenyl N-methyl-carbamate.

In the title compound, C(11)H(15)NO(3), the mean planes of the carboxamide and isopropyl groups are inclined at 109.9 (1) and 128.7 (2)°, respectively, to the mean plane of the phen-oxy group. In the crystal structure, mol-ecules are stacked along the b axis, without any π-π inter-actions. The stacked columns are linked together by inter-molecular N-H⋯O hydrogen bonds, with an N⋯O distance of 2.842 (2) Å.

4-(4-Ethoxy-benz-yl)-1,3-oxazolidin-2-one.

In the title compound, C(12)H(15)NO(3), the ethoxy-benzyl ring plane forms a dihedral angle of 60.3 (4)° with the mean plane of the oxazolidine ring. The mol-ecules are linked through N-H⋯O hydrogen bonds into a chain running in the b direction.

Isobutyl 3,5-dinitro-benzoate.

In the structure of the title compound, C(11)H(12)N(2)O(6), the mol-ecules are stacked along the b axis without any π-π inter-actions. The stacked columns are linked together by non-classical inter-molecular C-H⋯O inter-actions,. In the molecule, the nitro groups make dihedral angles of 9.4 (5) and 10.3 (5)° with the benzene ring.