Abstract

The complex adipose organ

It has highly plasticproperties to reprogram its genes and transdifferentiate reversibly into cells with different structure and functions.The adipose organ plays important role in health and disease states including obesity and MetS and fulfils several crucial survival needs like thermogenesis, storage of energy and fuel for metabolism, immune responses, sexual development around puberty, reproductive function and lactation. Further, as an endocrine organ, it secretes several peptides termed adipokines, including adiponectin and leptin.

Adiposity and metabolic mechanisms

The rising prevalence of obesity and MetS in recent decades reflects increased calorie consumption though diets rich in fat and refinedcarbohydrates, leading to over-nutrition and nutrient overload which in due course leads to nutritional toxicity, endangering the intracellular organelle and impairing intracellular and intercellular metabolic processes. The adipose tissue protects the vital organs through expansion of the WAT, through an upsurge in the adipocytecellsize and formation of new white adipocytes, and adiposity can, thus, be regarded a way to deal with nutritional excess.The IR linked to adiposity can also be regarded a measure to control excess nutrients entry into cells, endangering vital intracellular organs.

The excess folic acid and obesity link

Folic acid influences energy aswell as lipid metabolism by modifying DNA synthesis and gene expressions and contributes to alterations in metabolism. In the animal model, the EFA with a HF diet were related to significant weight and fat mass gain. Thus, EFA may intensify weight increase, adiposity and inflammatory response in setting of increased fat dietary intake.

Metabolic fallouts of adiposity/obesity

The adipose tissue relates to about 20% of body weight in lean individuals and to 50% or more body weight in extremely obese. The adipose tissue organ has white, beige and brown adipocytes for specialized functions, and their coordinated action ensure an optimal metabolic homeostasis. The adiposity is a crucial factor in development of metabolic diseases including DM, and high BMI, T2DM and IR are closely linked.With obesity, the levels of NEFAs, adiponectins, cytokines and proinflammatory markers like NNF-α and IL-6 involved in the genesis of IR, are increased, and with metabolic dysfunctions, there occur derangements of carbo-lipid and global metabolic homeostasis. Normally, there is a dynamic feedback relationship between β-cells function and insulin-sensitive response in tissues. The failure of the intricate process and sustained decline in β-cell function result in dysregulation of glucose levels and worsening ofT2DM.

Future projections and options

Both obesity and T2DM represent a global public health crisis brought about by rapid westernization, nutritional alterations transition and increasingly sedentary lifestyles. Controlling and treating Obesity as well as T2DM and their fallouts require a thoughtful long-term planning and rational use of limitedresourcesin developing countries with scarce resources. Further, owing to the wide range of therapeutic interventions and options available, the treatment algorithm is ridden with complexity.

Keywords Adiposity; Obesity; Adipose tissue; Metabolic syndrome; T2DM; Insulin resistance; Folic acid

Abbreviations: AD: Alzheimer’s Disease; AdipoQ: Adiponectin or Adipocyte Complement-Related Protein; AdipoQ gene: APM1, Mapped to Chromosome 3q27; AFA: Adequate Folic Acid; AMPK: Activated Mono Protein Kinase; ATP: Adenosine Tri Phosphate; BAT: Brown Adipose Tissue; BFD: Body Fat Distribution; BLAs: Brown-Like Adipocytes; BMI: Body Mass Index; β-cells:β-cells of Islets of Langerhans;β-3 Ars:Beta3 Adrenoreceptors; 11βHSD-1: 11β-Hydroxy Steroid Dehydrogenase Type 1; CLSs: Crown Like Structures; CNS: Central Nervous System; COX2: Cyclooxygenase 2; CVD: Cardio Vascular Disease; cAMP: Cyclic Adeno Mono Phosphate; DM: Diabetes Mellitus; EFA: Excess Folic Acid; ERK: Extracellular Signal Regulated Kinase; FFA: Free Fatty Acids; FGF21: Growth Factor; FOXC2: Fork Head Box Protein C2; HF-EFA:High Fat-Excess Folic Acid; IL-1α: Interleukin1α, IL-6: Interleukin-6; IR: Insulin Resistance; LPS: Lipo Poly Saccharide; MetS: Metabolic Syndrome; mRNA: Messenger-RNA; MHO: Metabolically Healthy Obese; PPARγ:Peroxisome Proliferator Activated Receptor-γ; Rb protein: Retinoblastoma Protein; SF:Subcutaneous Fat; ss3AR: Specific Adeno Receptor; S100-B: S100 Calcium Binding Protein B; SOCS-3: Suppressorof Cytokine Signaling; Smad3: Component of the TGFβ signaling pathway; TGFβ: Transforming Growth Factor Beta; T1DM: Type 1 Diabetes Mellitus; T2DM: Type 2 Diabetes NMellitus; TH:Tyrosine Hydroxylase;TNF-α:Tumour Necrosis Factor Alfa;TZDs: Thiazolidinediones; UCP1: Uncoupling Protein 1; VF: Visceral Fat; WAT: White Adipose Tissue