However, it cannot be overlooked that vitamin D deficiency may contribute to worsening cardiovascular health in obesity through several direct mechanisms, including activation of the renin-angiotensin-aldosterone system, which can predispose obese individuals to hypertension and left ventricular hypertrophy or an increase in the parathyroid hormone, which increases insulin resistance, downregulation proinflammatory cytokines and metalloproteinases, upregulation of anti-inflammatory cytokines, and inhibitors of metalloproteinases [41,42]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.