This document summarizes research on the browning of white adipose tissue by gut microbiota. It describes white adipose tissue and its functions, as well as gut microbiota and their impact on host metabolism. Specifically, it discusses how gut microbiota modulate white adipose tissue through the production of metabolites and components that promote browning. Studies in mice found that microbiota depletion increased browning, while certain bacteria and their short chain fatty acid products were linked to higher browning and improved metabolic outcomes in mice and some human studies. The document reviews various mechanisms and factors involved in the relationship between gut microbiota and white adipose tissue browning.

1. BROWNING OF WHITE ADIPOSE
TISSUE BY GUT-MICROBIOTA
BY
PALADI RAMYA
2020MSSB007
M.SC SPORTS BIOCHEMISTRY
CENTRAL UNIVERSITY OF RAJASTHAN
UNDER GUIDANCE OF
Dr. SHAILENDRA PRATAP SINGH

2. WHITE ADIPOSE TISSUE
 White adipose tissue (WAT) refers to a type of loose connective tissue
composed of white, lipid-filled cells.
*WAT is the most common type of adipose tissue in the body. 20% of the
total weight of a man is White adipose tissue.
* Theyhave receptorsfor insulin, sex hormones, nor epinephrine,
and glucocorticoids.
* White adipose tissue isused for energystorage. Upon releaseof
insulin fromthepancreas, white adiposecells' insulin receptorscause a
dephosphorylation cascadethat leadstothe inactivation of hormone-
sensitive lipase.
Trigger
Glucagon Glycogenolysis and glucogenesis
(in liver)
*The triggers for this process in white adipose tissue is adrenocarticotropic
harmone, adrenaline and noradrenaline.

3. • The hormone leptin is primarily manufactured in the adipocytes of white
adipose tissue, which also produces another hormone, asprosin.
• DEVELPOMENT:-
In humans, white adipose tissue starts to develop during early to mid-
gestation period.
* White adipose tissue consists of white adipocytes, which are the lipid
storage cells. They are differentiated from undifferentiated preadipocytes
through transcriptional cascade.
*This process is regulated by the nuclear receptor peroxisome proliferator-
activated receptor γ (PPARγ), a protein regulating gene involved in
regulation of fatty acid storage and glucose metabolism and members of
the CCAAT/enhancer-bindingprotein family, type of transcription
factors that promotes gene expression.
* PPARγ is required for both the adipogenesis and maintenance of the
adipocytes.

5. GUT-MICROBIOTA
• Gut microbiota are the microorganisms including bacteria, and archaea that
live in the digestive tracts of vertebrates including human and insects.
*The gastrointestinal metagenome (sometimes defined as the microbiome) is
the aggregate of all the genomes of gut microbiota.
*In the human, the gut is the main location of human microbiota.
• The gut microbiota has broad impacts,
1. Including effects on colonization,
2. Resistance to pathogens,
3. Maintaining the intestinal epithelium,
4. Metabolizing dietary and pharmaceutical compounds,
5. Controllingimmune function, and
6. Even behavior through the gut-brain axis.
EXAMPLES OF GUT MICROBIOTA:- Bacteroides fragilis, Bacteroides
melaninogenicus, Enterobacter sp. Pseudomonas aeruginosa, Faecalibacterium
prausnitzii, Peptococcus sp. Peptostreptococcus sp.etc.,

6. THE MAIN BACTERIAL PHYLA IN GUT ARE 6:-
• 1. Firmicutes (gram positive){ex- colistridium, mycoplasma and
bacillus}.
2.Bacteroidetes(gram negative){bacteroides and prevotella}.
3.Actinobacteria (gram-positive){bifidobacterium}.
4. Proteobacteria
5.Verrucomicrobia
6. Fusobacteria.

8. GUT MICROBIOTA ON WHITE ADIPOSE TISSUE
*Gut microbiota is an important modulator of host metabolic
homeostasis and energy balance.
*Gut microbiota activity results in the production of specific
microbial-derived metabolites (short-chain fatty acids) and structural
components (LPS and peptidoglycans), named postbiotic components.
*The gut microbiota is also an important endogenous factor
modulating BAT activity and browning of WAT.
*Microbiota depletion promoted the development of functional WAT
browning in subcutaneous and visceral fat depots, increasing
expression of brown fat markers (Ucp1, Cidea, Pgc1a, Ppara).

9. MITOPHAGY
UCP-1 Expression
WHITENING
BROWNING
WHITE ADIPOCYTE Cold BROWN ADIPOCYTE
cytokine(IL-18) UCP-1 EXPRESSION
Myokine(irisin) LIPOGENESIS
Gut microbiota OXIDATIVE STRESS
Proinfammatory cytokines(IL-6),oxidative stress

10. • EFFECTS OF INTERMITTENT FASTING:-
*The importance of gut microbiota on caloric restriction-metabolic
improvement demonstrating compositional and functional changes in
gut microbiota that were required to promote browning of WAT
and associated metabolic improvements.
*During caloric restriction, reduced LPS atten- uated inflammatory
process in WAT, increasing browning and insulin sensitivity, whereas
the reconstitution of LPS prevented these positive effects on
metabolism.
*In fact, geneteic and pharmacological depletion of LPS-TLR4
signalling pathway resulted in decreased WAT inflammation in
parallel to increased WAT browning, and improved insulin sensitivity
and hepatic steatosis .

12. Gut microbiota - WAT browning relationship in humans
• In obese pa- tients, Firmicutes family Ruminococcaceae, which is also in-
creased after cold exposure, was associated with elevated plasma acetate
levels, and was positively linked to the expres- sion of PRDM16,a marker
of beige/brown adipocytes, in subcutaneousWAT and insulinsensitivity .
*Acetate in- creases the activity of brown fat and induces the formation of
“beiges adipocytes”.
*An important consideration in humans is the extremely low expression of
brown/beige adipose tissue markers, indicating that browning of WAT in
humans may have less relevance than in mice
*In fact, the positive effects of diet-induced weight loss were not associat-
ed with the expression of brown/beige-related genes in human subcutaneous
WAT [94].

15. THANK YOU