Adipose Tissue

Slide 1 · Adipose Tissue

White and brown adipose tissue

Endocrine signalling, energy homeostasis and inflammation

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish the physiological roles of white and brown adipose tissue.

Explain how adipocyte-derived leptin and adiponectin influence energy balance.

Connect adipose-derived inflammatory mediators with obesity-associated systemic inflammation.

Integrate adipose, hypothalamic and immune pathways in clinicopathologic scenarios.

Slide 3 · Adipose tissue is a functional organ

Energy reservoir

Fat stores convey information about available energy.

Endocrine tissue

Adipocytes release leptin, adiponectin and other mediators.

Thermogenic tissue

Brown adipose tissue converts energy into heat.

Immune interface

Cytokines and immune cells influence adipose function.

Slide 4 · Two adipose tissues, two primary functions

Feature

White adipose tissue

Brown adipose tissue

Key role

Energy storage and endocrine signalling

Energy expenditure as heat

Mediators / mechanism

Leptin, adiponectin, cytokines, chemokines

Nonshivering thermogenesis

Clinical context

Metabolic and inflammatory responses

Energy balance and heat production

Slide 5 · Energy storage and energy balance are coupled

Adipose energy stores

Peripheral adiposity signals

Hypothalamic integration

Food intake and expenditure

Fat stores are not inert: Changing energy reserves alter the signals received by the brain.

Slide 6 · Fat quantity and fat distribution are distinct

Total adiposity

Body mass index is widely used as a practical measure of excess body weight.

BMI does not identify the anatomical distribution of fat.

Fat distribution

The textbook distinguishes central/visceral accumulation from subcutaneous accumulation.

Visceral predominance is associated with greater disease risk.

Slide 7 · Visceral adipose tissue has greater risk association

Central fat accumulation

Fat in trunk, mesentery and around viscera

Higher association with metabolic disease

The anatomical pattern of excess adiposity can matter beyond its overall quantity.

Slide 8 · Body weight depends on intake and expenditure

Energy intake

Eating behavior is regulated by neural and hormonal inputs.

Anabolic circuits favor food intake.

Energy expenditure

Catabolic circuits reduce intake and raise expenditure.

The balance of the two circuits helps stabilize body weight.

Slide 9 · The hypothalamus integrates peripheral information

Fat, gut and pancreas

Afferent hormonal signals

Arcuate hypothalamic neurons

Behavioral and metabolic output

The central processing system interprets signals about nutrient availability and body energy stores.

Slide 10 · The adipose-derived endocrine signal: Leptin

Production

Leptin is secreted by adipocytes.

Input variable

Secretion tracks the adequacy of fat stores.

Target

The hormone acts on hypothalamic circuits.

Net function

It restrains food intake and facilitates energy expenditure.

Slide 11 · Leptin output reflects fat stores

Greater adipose stores

Greater leptin secretion

Hypothalamic satiety signalling

Reduced drive to eat

This is a feedback relationship; It does not imply that all obesity states remain leptin-responsive.

Slide 12 · Low energy stores reduce leptin feedback

Reduced fat stores

Reduced circulating leptin

Increased orexigenic influence

Increased food intake

The response favors restoration of energy reserves during an energy deficit.

Slide 13 · Leptin acts beyond the adipocyte

Leptin enters blood

Crosses blood–brain barrier

Acts in hypothalamus

Adjusts intake and expenditure

The hypothalamus is the main integrating site.

Slide 14 · Two arcuate neuronal populations respond to leptin

POMC / CART neurons

Activated by leptin.

Promote catabolic, anorexigenic output.

NPY / AgRP neurons

Inhibited by leptin.

Ordinarily promote feeding and anabolic output.

Slide 15 · POMC/CART neurons are the appetite brake

Leptin input

POMC/CART activation

α-MSH generation

MC3/4 receptor signalling

Following food intake, POMC cleavage yields α-melanocyte-stimulating hormone (α-MSH).

Slide 16 · Melanocortin signalling produces catabolic output

α-MSH

MC3/4 receptors

Second-order pathways

Less intake + more expenditure

BDNF, TRH and CRH among mediators of second-order catabolic signalling.

Slide 17 · NPY/AgRP neurons act as an appetite accelerator

Fasting state

NPY/AgRP activation

NPY → Y1/Y5 receptors

Increased food intake

An orexigenic response conserves and replenishes energy stores.

Slide 18 · Anabolic circuits also conserve energy

NPY/AgRP output

Second-order anabolic signals

Reduced sympathetic output

Reduced energy expenditure

Downstream anabolic effects with MCH and orexin signalling.

Slide 19 · NPY/AgRP inhibits the opposing neuronal arm

NPY/AgRP activity

Direct inhibition of POMC/CART

Reduced anorexigenic signalling

Feeding drive predominates

The reciprocal relationship strengthens the central response to fasting.

Slide 20 · The two hypothalamic arms oppose one another

System

Catabolic arm

Anabolic arm

First-order neurons

POMC/CART

NPY/AgRP

Second-order signal

MC3/4 receptor pathway

Y1/Y5 receptor pathway

Effect on food intake

Decreases

Increases

Effect on energy expenditure

Increases

Decreases

Slide 21 · Stable weight reflects balanced central signalling

Peripheral energy-state signals

Opposing central circuits

Integrated efferent response

Relative stability of energy stores

The “lipostat” is a regulatory model for maintaining energy homeostasis, not a single anatomical structure.

Slide 22 · Leptin modulates energy expenditure

Appetite

Suppresses intake through hypothalamic circuits.

Activity

Abundant leptin stimulates physical activity.

Heat

Supports thermogenesis and heat production.

Metabolic output

Promotes overall energy expenditure.

Slide 23 · Sympathetic nerves connect brain and adipose tissue

Hypothalamic output

Sympathetic nerve activity

Norepinephrine release in adipose

Thermogenic response

This as a component of leptin-related heat production.

Slide 24 · Leptin pathway genetics establish causal importance

Leptin loss of function

Insufficient adiposity signal despite energy stores.

Leptin receptor loss

Signal cannot be interpreted normally.

MC4R loss of function

Disrupts downstream melanocortin signalling.

Phenotype

These monogenic abnormalities may cause severe obesity.

Slide 25 · Leptin deficiency mimics a starvation signal

Disabled leptin gene

Brain fails to sense sufficient stores

Persistent feeding drive

Severe obesity

This principle using mouse models and rare human mutations.

Slide 26 · Leptin-receptor defects disrupt feedback

Leptin is present

Defective receptor function

Impaired central adiposity sensing

Severe obesity phenotype

Secretion of a hormone and biological response to that hormone are separate steps.

Slide 27 · MC4R loss of function implicates downstream signalling

Upstream adiposity signals

Melanocortin pathway

MC4R loss of function

Impaired catabolic feedback

MC4R loss-of-function mutations in a subset of patients with massive obesity.

Slide 28 · Leptin resistance differs from leptin deficiency

Feature

Leptin deficiency

Leptin resistance

Circulating leptin

Deficient

May be high in obesity

Biological problem

Insufficient hormonal signal

Blunted response to signal

Interpretation

Defective signal production

Impaired response despite signal

Slide 29 · Why more leptin does not always suppress appetite

Large adipose stores

Elevated leptin concentration

Reduced anorexigenic responsiveness

Continued obesity

Leptin resistance as a limitation of leptin administration in common obesity.

Slide 30 · Insulin contributes to central appetite regulation

Leptin

Secreted by fat cells.

Presented as the principal adiposity signal.

Insulin

Secreted by pancreas.

Receptors occur on POMC/CART and NPY/AgRP neurons; Also anorexigenic.

Slide 31 · Adiponectin: A second major adipokine

Source

Produced in adipose tissue.

Fatty acids

Promotes oxidation in skeletal muscle.

Glucose

Reduces hepatic glucose production.

Insulin action

Increases insulin sensitivity.

Slide 32 · Adiponectin enhances fatty-acid utilization

Adiponectin release

Skeletal-muscle action

Increased fatty-acid oxidation

Reduced fatty-acid levels

The pathway links adipose-derived signalling to peripheral fuel use.

Slide 33 · Adiponectin reduces hepatic glucose output

Adipose-derived adiponectin

Action on liver

Less hepatic glucose production

Improved metabolic regulation

This is one of the mechanisms associated with increased insulin sensitivity.

Slide 34 · Adiponectin supports insulin sensitivity

Muscle

Stimulates fatty-acid oxidation.

Liver

Reduces glucose production.

Whole-body effect

Improves insulin responsiveness.

Clinical linkage

Supports protection against metabolic dysregulation.

Slide 35 · Adiponectin concentrations vary with adiposity

Lean individuals

The text describes higher circulating adiponectin than in obesity.

Effects include improved fuel handling.

Individuals with obesity

Adiponectin levels tend to be lower.

Loss of its beneficial actions may accompany metabolic dysfunction.

Slide 36 · Adiponectin effects extend beyond metabolism

Inflammation

Anti-inflammatory actions.

Blood vessels

Antiatherogenic actions.

Cell proliferation

Antiproliferative actions.

Heart

Cardioprotective actions.

Slide 37 · Two adiponectin receptors distribute signaling

AdipoR1

Highly expressed in skeletal muscle.

Receptor for adiponectin-mediated metabolic signalling.

AdipoR2

Highly expressed in liver.

Receptor for adiponectin-mediated metabolic signalling.

Slide 38 · Adiponectin links receptors to lipid metabolism

Adiponectin binding

AdipoR1 / AdipoR2 signalling

Inhibition of fatty-acid synthesis pathway

Shift in lipid handling

Acetyl-CoA carboxylase inactivation as a downstream consequence; Detailed kinase intermediates are omitted here.

Slide 39 · Free fatty acids may influence hypothalamic signaling

Excess circulating fatty acids

Entry into hypothalamus

Microglial sensing

Inflammatory mediators

This is presented as evidence suggesting a contributory route, not as a complete established mechanism.

Slide 40 · Hypothalamic inflammation may blunt leptin action

Microglial inflammatory mediators

Actions on hypothalamic neurons

Reduced leptin responsiveness

Weakened antiadiposity signals

The proposed link is mechanistic and framed cautiously.

Slide 41 · Adiponectin may counter a lipid–inflammation loop

Adiponectin activity

Lower fatty-acid burden

Less proposed microglial activation

Support for leptin responses

Inferred integration of the textbook pathways; Not a clinical treatment claim.

Slide 42 · White adipose tissue has a diverse secretome

Adipokines

Leptin and adiponectin.

Cytokines

TNF, IL-6, IL-1 and IL-18.

Chemokines

Inflammatory cell–recruiting signals.

Steroid hormones

Additional endocrine products.

Slide 43 · Adipose-derived cytokines signal beyond fat

TNF

Listed as an adipose cytokine.

IL-6

Contributes to inflammatory signaling.

IL-1

Part of the adipose cytokine repertoire.

IL-18

Included in the adipose proinflammatory mediator profile.

Slide 44 · Chemokines broaden adipose–immune communication

White adipose tissue

Chemokine output

Immune-cell interactions

Altered local inflammatory milieu

The source identifies chemokine production and immune reciprocity; This is a conceptual integration.

Slide 45 · White adipose also produces steroid hormones

Endocrine identity

White fat synthesizes and releases steroid hormones in addition to adipokines.

Its biology is therefore not restricted to energy storage.

Systems implication

Adipose influences metabolism and systemic signaling.

Specific steroid pathways are outside this subsection.

Slide 46 · Obesity-associated adipose inflammation is systemic

Increased adipose cytokines

Increased inflammatory signalling

Chronic proinflammatory state

Higher circulating CRP

CRP is as a marker of the chronic proinflammatory state in obesity.

Slide 47 · CRP is a systemic marker, not an adipokine

Component

Source / class

Teaching interpretation

TNF, IL-6, IL-1, IL-18

Adipose-associated cytokines

Upstream inflammatory mediators

Chemokines

White-adipose mediators

Recruitment / immune communication

C-reactive protein

Circulating inflammatory marker

Evidence of systemic inflammatory state

Slide 48 · Macrophages participate in adipose regulation

Resident tissue macrophages

Signals within adipose tissue

Changes in adipocyte function

Metabolic–immune feedback

The text identifies macrophage function as an emerging, reciprocal influence.

Slide 49 · T cells contribute to adipose–immune crosstalk

Adipose → immune cells

Cytokines and chemokines affect immune pathways.

The tissue promotes a proinflammatory milieu in obesity.

Immune cells → adipose

Some T cells influence adipocyte function.

Evidence for reciprocal regulation.

Slide 50 · Inflammation is not a one-directional pathway

Adipocyte mediator secretion

Macrophage / T-cell activity

Regulatory feedback to adipocytes

Persistent tissue interaction

An original conceptual schema of the bidirectional signaling.

Slide 51 · White adipose integrates three systems

Lipid metabolism

Storage and use of energy substrates.

Nutrition

Signals about sufficiency of energy stores.

Inflammation

Cytokines, chemokines and immune-cell regulation.

Systemic physiology

Endocrine effects on multiple organs.

Slide 52 · Brown adipose tissue generates heat

Brown adipose tissue

Energy-generating reactions

Uncoupling from storage

Heat production

The defining function is nonshivering thermogenesis.

Slide 53 · Thermogenesis is distinct from energy storage

Physiological route

Energy fate

Dominant tissue context

Energy conservation

Stored for later use

White adipose tissue

Nonshivering thermogenesis

Released as heat

Brown adipose tissue

Whole-body relevance

Energy balance

Intake–expenditure regulation

Slide 54 · Brown adipose is prominent in newborns

Newborn pattern

Brown adipose tissue is abundant early in life.

Prominent deposits occur in interscapular and supraclavicular regions.

Physiological meaning

Nonshivering thermogenesis permits energy expenditure as heat.

No shivering is needed for this mechanism.

Slide 55 · Brown adipose has several described locations

Principal regions

Interscapular and supraclavicular.

Perivisceral regions

Around kidneys and aorta.

Thoracic / cardiac regions

Around heart and trachea.

Other reported site

Around pancreas.

Slide 56 · Brown adipose tissue can persist into adulthood

Earlier view: Loss after infancy

Imaging of adolescents and adults

Residual brown adipose detected

Potential thermogenic relevance

The original text reports persistence demonstrated by imaging rather than quantitative prevalence.

Slide 57 · Thermogenic activation is under investigation

Preservation

How can brown adipose tissue be retained or maintained in adulthood?

This is a research direction, not an established intervention in this subsection.

Activation

Can preserved brown adipose increase expenditure of energy as heat?

The textbook frames activation as an area of active investigation.

Slide 58 · White and brown adipose have complementary roles

Dimension

White adipose

Brown adipose

Physiological priority

Stores fuel; senses fuel stores

Dissipates energy as heat

System communication

Hormones and inflammatory mediators

Neural thermogenic responsiveness

Clinical insight

Adiposity and inflammation

Potential energy-expenditure lever

Slide 59 · Case: High leptin does not imply intact satiety

An adult with obesity has abundant fat stores but does not show an appropriately strong anorexigenic response to adiposity signals.

What mechanism reconciles large fat stores with continuing feeding drive?

Interpretation: Leptin resistance — response is blunted despite high leptin in obesity.

Slide 60 · Case: Fat distribution alters risk interpretation

Two adults have similar overall excess body weight. One has predominantly visceral fat; The other mainly subcutaneous accumulation.

Why can their disease risk differ despite comparable overall adiposity?

Interpretation: Central/visceral distribution carries a stronger association with several obesity-related disorders.

Slide 61 · Adipose endocrine and immune pathways converge

Signal of energy stores

Leptin communicates adiposity to the hypothalamus.

Metabolic protection

Adiponectin supports lipid oxidation and insulin sensitivity.

Inflammatory signals

White adipose cytokines and chemokines link to CRP.

Energy dissipation

Brown adipose performs nonshivering thermogenesis.

Slide 62 · Core principles for pathology teaching

Adipose tissue influences both energy balance and systemic inflammatory biology.

White adipose tissue releases leptin, adiponectin, cytokines, chemokines and steroid hormones.

Brown adipose tissue uses nonshivering thermogenesis; Some persists in adults.

Feedback failure, altered adipokines and immune-cell interactions help explain metabolic effects of obesity.

Slide 63 · Primary source and scope

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th ed. (2026). Chapter 9: Environmental and Nutritional Diseases.

“Adipose Tissue,” p. 407, with surrounding “Obesity,” “Leptin” and “Adiponectin” material, pp. 404–407.

The primary source discussion spans the sections “Obesity,” “Leptin,” “Adiponectin” and “Adipose Tissue.”

For the central energy-balance circuitry, see the textbook’s Figure 9.28.