Saturated fatty acids (SFAs) are known to induce inflammation and insulin resistance in adipocytes through toll-like receptor-4 (Tlr4) signaling, but the mechanisms are not well delineated. Furthermore, the potential roles of Tlr2 and the c-Jun N-terminal kinase (JNK) in inflammation in adipocytes have not been investigated. We demonstrated that palmitate, lipopolysaccharide (LPS), and the toll-like receptor-2 (Tlr2) agonist, zymosan A (ZymA), induced insulin resistance in a time- and dose-dependent manner in 3T3-L1 adipocytes. Corresponding with the reduction of insulin sensitivity was an increased expression of IL-6, as well as activation of the proinflammatory transcription factors, nuclear factor kappa B, and activator protein-1. Reactive oxygen species (ROS) accumulation was also observed in palmitate and Tlr agonist treated adipocytes. The JNK inhibitor, SP600125, attenuated insulin resistance mediated by SFA and Tlr agonists, which corresponded with a diminished proinflammatory response and reduced ROS accumulation. Collectively, these results demonstrated Tlr2 involvement in adipocyte inflammation and therefore implicated the receptor as a potential target for SFA. Moreover, activation of JNK also appeared to be essential to Tlr2-, as well as Tlr4-induced insulin resistance and oxidative stress.

Adiponectin is an adipocyte-derived hormone that has been implicated recently in the regulation of inflammation in immunocytes, and in lipid metabolism and glucose homeostasis in liver, skeletal muscle and adipocytes. However, information in non-rodent models is limited. We have cloned and sequenced the porcine adiponectin open reading frame and evaluated the regulation of adiponectin in vivo following lipopolysaccharide (LPS) or E. coli administration. The porcine sequence shares approximately 88, 86, 85 and 83% homology with the dog, human, cow and mouse adiponectin respectively, and 79-83% similarity with dog, human, cow and mouse proteins at the amino acid level, based on the translated porcine sequence and GenBank submissions for the other species. Relative serum adiponectin concentrations were not altered in pigs infused with E. coli, and mRNA expression in adipose tissue was not responsive to LPS. However, analysis of serum from very lean vs a substantially fatter genotype of pig indicated that relative circulating adiponectin concentrations are higher (P,0·01) in the lean pigs than in the fatter genotype, and that the difference is established relatively early in the growth curve. Also, incubating pig adipocytes for 6 h with recombinant pig adiponectin resulted in an approximately 30% reduction (P,0·05) in lipogenesis compared with adipocytes under basal conditions and with those incubated in the presence of insulin. This is the first report in any species that adiponectin antagonizes the incorporation of glucose carbon into lipid in the adipocyte, and provides additional evidence that adiponectin acts as an autocrine regulatory factor to regulate energy metabolism.

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The relationship between obese gene expression and energy intake was determined in pigs of various body weights. With ad libitum consumption, expression increased (P < 0.001) with body weight from 55 to 163 kg. Obese mRNA relative abundance was correlated with fat mass (r = 0.74, P < 0.0001) and percentage of fat (r = 0.72, P < 0. 0001). Obese expression was also evaluated at 159 kg (initial weight) and ad libitum, maintenance or 23% of maintenance intake for 28 d. Obese mRNA was independent of treatment (P > 0.78) despite considerable weight differences. Obese mRNA abundance was then compared at 136 kg (initial weight) and ad libitum or maintenance intake for 3 or 28 d. Abundance was not influenced by either duration of treatment or intake, despite a small increase (P < 0.01) in serum nonesterified fatty acids (NEFA) and a reduction (P < 0.02) in insulin attributable to maintenance intake. Finally, mRNA abundance was determined at 60 and 136 kg and conditions of food deprivation or ad libitum intake for 3 d. Food deprivation reduced (P < 0.01) serum insulin and increased (4- to 5-fold) NEFA concentrations. Obese mRNA abundance was greater (P < 0.01) in the heavier pigs and was reduced (P < 0.01) by food deprivation. We conclude that obese mRNA abundance in pigs correlates with fat mass and percentage of body fat under conditions of ad libitum intake. Furthermore, obese mRNA abundance is reduced by food deprivation, whereas lesser degrees of intake restriction do not change obese mRNA abundance, even when accompanied by appreciable weight loss.

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