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514 Cardio Diabetes Medicine 2017

Convertible Visceral Fat As a

Therapeutic Target to Curb Obesity

Dr. P.G. Sundararaman M.D., D.M.
Consultant Endocrinologist

ABSTRACT requirements for thermo genesis. Hypertrophic vis-
ceral adipocytes are characterized by a hyperlipolytic
Obesity worldwide is increasing in epidemic propor-
tion affecting 13 % of the population. Obesity is form state that is resistant to the anti-lipolytic effect of in-
of inflammation, increasing the risk of various health sulin. The resulting overload of free fatty acids, glyc-
problems. Obesity is associated with poor quality of erol and lactate in the liver adversely affects hepatic
life and premature death. Adults with extreme obesi- metabolism, leading to increased liver glucose and
ty have increased risks of dying at a young age from triacylglycerol rich lipoprotein production. Moreover,
cancer and many other causes including heart dis- white adipocytes are endocrine cells that release
ease, stroke, diabetes, kidney and liver diseases. The hormones such as leptin and adiponectin, as well
researchers found that the number of years of life as pro-inflammatory cytokines, including interleu-
lost for class III obesity was equal or higher than that kin-6 (IL-6) and tumour necrosis factor. The greater
of current cigarette smokers among normal-weight production and secretion of IL-6, IL-8, plasminogen
participants in the same study. In the early 1980s, activator inhibitor 1 and angiotensinogen by visceral
cross-sectional clinical studies showed a higher in- fat relative to subcutaneous fat may also account for
cidence of hypertension, hypertriglyceridaemia, and the harmful effects of visceral obesity.
hyperinsulinemia and glucose intolerance in individ- The main target of anti-obesity strategies is the con-
uals with a high waist/hip ratio. version of white adipocytes to brown ones. Evolution
Three types of adipose tissue are present; these are of this transdifferentiation started several centuries
white, brown and beige. The main function of the for- before. Tibetian yoga- means the fierce goddess of
mer is to store excess energy in the form of TAGs heat and passion in Tibetan Buddhist tradition. Med-
(triacylglycerol), whereas the latter is specialized to itation, Breathing exercises, Extreme cold exposure
dissipate energy as heat through UCP1 (uncoupling caused the conversion of white adipocytes to brown
protein 1)-mediated uncoupling of oxidative phosphor- ones
ylation from ATP synthesis ; Beige adipocytes could Some of the agents, such as PPARγ activator rosigl-
be perceived as the result of ‘transdifferentiation’ of itazone induce the expression of UCP1.Activation of
WAT to BAT in response to appropriate stimuli, a re- PPARγ induces brown adipocyte-like cells in mouse
cent study suggests that beige adipocytes are a new epididymally derived white preadipocytes differentiat-
type of adipocytes derived from progenitors distinct ed to mature adipocytes in vitro. PRDM16 is involved
from WAT and BAT. WAT, which is highly inflamed in in both the induction of BAT genes and the repres-
obese individuals (metainflammation) and is closely sion of WAT genes. PRDM16 induces 200-fold UCP1
involved in the onset of some of the more severe and also strongly induces PGC-1a. PRDM16 functions
medical complications of obesity. In obesogenic synergistically with PPARγ.
conditions, WAT is infiltrated by macrophages that
form crown-like structures around dying adipocytes. C/EBPβ acts in synergy with PRDM16. Inhibition of C/
This phenomenon is highly pro-inflammatory and is EBPβ forces adipocyte precursors to acquire a white
one of the pivotal events leading to insulin resistance phenotype during development. Countering such in-
and type 2 diabetes. Adipocytes therefore have the hibition can promote browning.
distinctive ability to physiologically and reversibly un- Empagliflozin Promotes Fat Utilization and Browning.
dergo phenotype reprogramming to meet the body’s
FXR agonist fexaramine (Fex) Adipocyte MR regu-

GCDC 2017