Weight Management and Obesity

How the Body Regulates Weight:

Body weight is not simply a matter of willpower — it’s a tightly regulated biological process controlled by the brain, particularly the hypothalamus. This system continuously processes information from hormones, nerves, and reward pathways to maintain energy balance. After weight loss, the body adapts by slowing metabolism and increasing hunger, making weight regain common. These changes reflect biology, not personal failure.

1. Genetic Factors

Our genes play a significant role in how body weight is regulated. Variations in certain genes, such as FTO and MC4R, can influence appetite, how efficiently calories are stored, and an individual’s natural “set point” for weight. Research involving twins and adoption studies shows that body mass index (BMI) is highly heritable — often reflecting biological rather than environmental influences.

2. Hormonal Regulation

Hormones communicate your body’s energy status to the brain. The hypothalamus interprets these messages to determine when you should eat and when to stop.

• Leptin and insulin send “I’m full” signals.
• Ghrelin triggers hunger before meals.
• Hormones such as GLP-1 and PYY promote fullness after eating.

When these signals are disrupted — due to stress, sleep loss, illness, or other factors — appetite control becomes more difficult.

3. The Role of the Hypothalamus

The hypothalamus acts as the body’s command centre for energy regulation. It receives and integrates input from several types of neurons:

• NPY/AgRP neurons stimulate hunger.
• POMC/α-MSH neurons promote satiety and reduce intake.

This balance determines not only how much food we eat but also how efficiently our body uses energy.

4. The Reward System and Eating for Pleasure

Eating is influenced by more than just energy needs. Palatable, high-calorie foods can activate the brain’s dopamine reward pathways, creating pleasure and reinforcing eating behaviours — even when we’re not physically hungry. This hedonic drive can override normal appetite regulation.

The Complexity of Weight and Obesity

Weight regulation is influenced by an intricate interaction between genes, hormones, neural circuits, and environmental factors. Stress, poor sleep, certain medications, hormonal changes (such as during menopause), gut microbiome health, and exposure to toxins can all affect appetite, metabolism, and fat storage. These influences don’t directly cause obesity but can make managing weight significantly harder.

 

Challenges That Disrupt Weight Regulation

Neuroendocrine and Medication-Related Factors

Certain medical conditions and medications — including antipsychotics, corticosteroids, insulin, and disorders like hypothyroidism, PCOS, or Cushing’s syndrome — can interfere with normal appetite and metabolism. They alter hormonal balance, reduce insulin sensitivity, and promote fat accumulation.

Stress, Sleep, and Circadian Disruption

Chronic stress triggers the HPA axis, elevating cortisol levels and increasing appetite while suppressing leptin.

Insufficient sleep reduces leptin and raises ghrelin, which amplifies hunger and cravings.

Shift work or disrupted circadian rhythms can further confuse the body’s internal hunger and fullness cues.

Gut Health and Viral Factors

An imbalance in the gut microbiome can influence how efficiently the body extracts and stores energy from food. A higher ratio of Firmicutes to Bacteroidetes has been associated with increased calorie absorption and low-grade inflammation, both of which may contribute to weight gain.

Additionally, certain viral infections such as Adenovirus-36 have been implicated in promoting fat cell development and lipid storage in a portion of individuals with obesity. In such cases, weight changes are not primarily driven by behaviour, but by biological alterations in energy regulation and fat metabolism.

Hormonal Changes and Environmental Influences

Hormonal transitions — particularly during menopause — lead to a natural decline in oestrogen. This shift can reduce spontaneous physical activity and redirect fat distribution toward the abdominal region.

Environmental chemicals known as endocrine disruptors (including BPA and DEHP, found in plastics, personal care products, and food packaging) may also interfere with hormone function. Their effects can persist over time and even influence future generations.

It’s important to recognise that not all changes in body weight stem from diet or lifestyle choices — some result from physiological transitions or hidden environmental exposures that alter the body’s natural regulatory systems.

 

Health Consequences of Obesity

Obesity affects far more than physical appearance. It impacts multiple organ systems — including metabolic, cardiovascular, respiratory, hormonal, and reproductive pathways. Early identification and intervention can reverse or reduce many of these complications, improving long-term health outcomes.

 

Common Comorbidities

Excess body weight is strongly linked with numerous health conditions. Key conditions often associated with obesity are:

Cardiometabolic Conditions:

Metabolic Syndrome

A cluster of interrelated metabolic disturbances — including hypertension, dyslipidaemia, central adiposity, and insulin resistance — that substantially increase the risk of cardiovascular disease, stroke, and type 2 diabetes.

This syndrome is highly prevalent in individuals with obesity but often underdiagnosed. Early detection enables timely intervention and improved outcomes.

Type 2 Diabetes & Prediabetes

Chronic disruptions in glucose regulation often progress silently. Identifying early markers of insulin resistance or impaired fasting glucose allows for lifestyle and pharmacological interventions that prevent long-term complications.

 

Endocrine Disorders

Polycystic Ovary Syndrome (PCOS)

A common endocrine disorder affecting women of reproductive age, closely associated with insulin resistance and metabolic dysfunction.

Up to 80% of women with obesity may have features of PCOS, which can contribute to infertility, irregular cycles, metabolic complications, and psychological distress.

 

Cushing’s Syndrome

A less common but serious condition caused by chronic exposure to excess cortisol. Unlike other conditions, it is typically a cause rather than a consequence of obesity.

Suspected cases require prompt endocrinology referral for specialist assessment.

Respiratory and Sleep-Related Disorders

Obstructive Sleep Apnoea (OSA)

OSA is a sleep disorder characterised by intermittent airway obstruction during sleep, leading to poor oxygenation, fragmented rest, and daytime fatigue.

It significantly worsens cardiovascular and metabolic health and is estimated to affect up to 60% of people living with obesity.

Liver & Gastrointestinal System | Genitourinary System

Non-Alcoholic Fatty Liver Disease (NAFLD)

A condition where excess fat accumulates in the liver, unrelated to alcohol intake.

Often asymptomatic, occurring in up to 70–90% of individuals with obesity.

If untreated, it can progress to liver inflammation, fibrosis, and eventually cirrhosis.

Male Hypogonadism

Characterised by reduced testosterone levels, which can affect libido, energy, and overall mood.

Frequently underdiagnosed in men with obesity, it contributes to impaired metabolic function and reduced quality of life.