Obesity is the primary cause of metabolic syndrome (MS), further developing to atherosclerosis, hypertension, insulin resistance and diabetes in different individuals depending on their predisposed genetic background. Though adipose tissue acts as endocrine gland, as storage for energy reserve and insulation to vital organs but overloaded adipose tissue, turns inflammatory and induces systemic low grade inflammation (LGI), affecting the normal physiology. The endothelial cells, the innermost layer of a blood vessel, are the most affected ones and responsible for micro and macro-vascular complications. Obesity is linked to dysfunction of endoplasmic reticulum and mitochondria in variety of cells resulting oxidative stress, accumulation of residual damaged cell organelles and ER stress leading to UPRs (unfolded protein responses) accumulation in the cytoplasm. This is also associated to low autophagy. The whole process activates the innate immunity and attracts macrophages towards adipose tissue and secretes abnormal adipokines and inflammatory cytokines. At physiological level it is manifested as changed neurological secretions, sleep pattern, appetite, and hunger signals. Thus, activation of antioxidant enzymes and autophagy by changed life style (sleep cycle resonance with circadian rhythm), regulation of digestive power and food habits (energy intake/expenditure balance), medicinal supplements (medicine and herbal) and behavioural changes (psychological and environmental factors) may prove effective in management of obesity and related complications. Here, we have discussed the etiological factors responsible behind the pathogenesis of MS and involved signaling pathways with reference to autophagy. INTRODUCTION: Obesity is a public health problem with continuous rising trend. In 2010, overweight and obese persons were estimated to cause 3.4 million deaths, 3.9% of years of life lost, and 3.8% of DALYs (disability adjusted life years) globally 1. Another study of 2015 indicates that, a total of 107.7 million children and 603.7 million adults were obese. High BMI accounted for 4.0 million deaths globally and its 40% occurred in persons who were not obese.