Therefore, the present study also assessed the possibility of a beneficial interaction between GO and PIO to reduce the TZD dose level to avoid long term undesirable effects. This is the first study that shows the positive effect of GO in treating MetS and its accompanied cardiometabolic risk factors. GO ameliorated fructose-induced obesity, dyslipidemia, hypertension, hyperuricemia, and hyperglycemia. It also improved insulin sensitivity, noted by the reduction of HOMA-IR index, with the concomitant enhancement of QUICK and McAuley indices with a better response to IPGTT. Furthermore, the monoterpene alcohol suppressed the fructose-mediated increase in HbA1c and RAGE, as well as oxidative/nitroactive stress. Moreover, GO modulated the assessed adipokines to reduce inflammation. The administration of GO up-regulated the transcription of PPAR-�� supporting, thus, a previous in vitro study. Wang et al. verified that the activation of PPAR-�� suppresses the ligand-RAGE activation of nuclear 6bK factor – ��B and, hence, its downstream events. Following chronic hyperglycemia, several RAGE ligands are formed including circulating advanced glycated end products and TNF-��. In a feed forward cycle, the ligand-RAGE signaling results in the up-regulation of RAGE along with the proinflammatory mediators, viz., IL-1�� and TNF-�� to promote the development of insulin resistance by disturbing insulin signaling. The ligand-RAGE induced inflammatory cascade deteriorates also endothelial function to participate in MetS associated hypertension, reported herein. Additionally, the current hyperglycemia resulted in the elevation of the long term glycemic control index HbA1c. Under a long-standing hyperglycemic condition, advanced glycated end products are formed that have been linked to the MetS mediated hypertension. The present improved insulin sensitivity and antihypertensive action of GO are consequences of reduced hyperglycemia and PPAR-�� activation to suppress proinflammatory mediators, RAGE, and HbA1c. The anti-inflammatory action of the monoterpene alcohol supports another experimental study. In acquiesce with the findings of Singh et al. GO decreased both of AST and ALT activities, indicating the overall suppression of the inflammatory process associated with fructose ingestion. The inhibition of ALT may be attributed to the suppression of TNF-��, up-regulation of PPAR- ��, and/or via increasing adiponectin, all of which participate in improving insulin signaling. Adiponectin is another adipocytokine that A 61603 hydrobromide increases peripheral glucose uptake and utilization. It acts in contrast to TNF-��, where Liang et al. displayed that this proinflammatory cytokine down-regulates adiponectin expression. In the current work, GO increased adiponectin to add to its insulin sensitizing effects.