Hypothalamic Obesity: Prologue and Promise

Abuzzahab, M. Jennifer; Roth, Christian

doi:10.1159/000496564

Cited by 53 publications

(50 citation statements)

References 64 publications

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“…Hypothalamic lesions can cause rapidly progressive, severe obesity, which is particularly difficult to treat 198 . Hypothalamic obesity can develop after traumas, tumours or inflammatory diseases perturbing hypothalamic function.…”

Section: Pathophysiology Of Obesity In Humansmentioning

confidence: 99%

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

Theilade

Christensen

Vilsbøll

et al. 2021

Diabetes Obesity Metabolism

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Obesity is one of the biggest health challenges of the 21st century, already affecting close to 700 million people worldwide, debilitating and shortening lives and costing billions of pounds in healthcare costs and loss of workability. Body weight homeostasis relies on complex biological mechanisms and the development of obesity occurs on a background of genetic susceptibility and an environment promoting increased caloric intake and reduced physical activity. The pathophysiology of common obesity links neuro‐endocrine and metabolic disturbances with behavioural changes, genetics, epigenetics and cultural habits. Also, specific causes of obesity exist, including monogenetic diseases and iatrogenic causes. In this review, we provide an overview of obesity mechanisms in humans with a focus on energy homeostasis, endocrine regulation of food intake and eating behavior, as well as the most common specific causes of obesity.

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Section: Pathophysiology Of Obesity In Humansmentioning

confidence: 99%

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

Theilade

Christensen

Vilsbøll

et al. 2021

Diabetes Obesity Metabolism

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Section: Introductionmentioning

confidence: 99%

“…Multiple therapies have been studied for HO 16 ; however, to date, none have proven to be both safe and effective. Stimulant medications with anorectic properties were not beneficial in decreasing body mass index (BMI) 16 . Medications targeting hyperinsulinism (octreotide, metformin) both as monotherapy and in conjunction with diazoxide or fenofibrate, have also failed to improve HO 16 .…”

Section: Introductionmentioning

confidence: 99%

A phase 3 randomized clinical trial using a once‐weekly glucagon‐like peptide‐1 receptor agonist in adolescents and young adults with hypothalamic obesity

Roth

Perez

Whitlock³

et al. 2020

Diabetes Obesity Metabolism

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Aim To evaluate the efficacy, safety and tolerability of a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) in patients with hypothalamic obesity (HO). Materials and Methods A two‐arm, randomized, multicentre, double‐blind, placebo‐controlled trial was conducted in 10‐ to 25‐year‐olds with hypothalamic injury following intracranial tumour and HO. Participants were randomized to once‐weekly subcutaneous injections of a GLP‐1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint was 36‐week % change in body mass index (BMI). Secondary outcomes included change in body composition (by dual energy x‐ray absorptiometry). Results Forty‐two participants were randomized to ExQW (n = 23) or placebo (n = 19). Participants were 5 ± 2 years (mean ± SD) postdiagnosis and development of HO (BMI 37.3 ± 7.1 kg/m2). In intention‐to‐treat analysis, the effect of 36‐week ExQW vs. placebo on % Δ BMI was not significant (estimated treatment difference −1.7 ± 1.8%, 95% CI −4.1 to 0.6%, P = .40); however, total body fat mass was reduced (estimated treatment difference −3.1 ± 1.4 kg, 95% CI −5.7 to −0.4 kg, P = .02). There was a significant reduction in waist circumference (estimated effect of treatment −3.5 [95% CI −5.5 to −1.6] cm, P = .004). All patients treated with placebo increased % of adipose tissue, while 50% treated with ExQW had reductions (P < .001). Mean HbA1c, glucose tolerance and serum lipids did not change significantly with therapy. ExQW was well tolerated. The most frequent adverse events were transient gastrointestinal disturbances (ExQW vs. placebo: nausea 6/23 vs. 3/18, vomiting 4/23 vs. 4/18 and diarrhoea 7/23 vs. 3/18). Conclusions GLP‐1 RAs are a promising and safe treatment to improve or stabilize HO in children and young adults.

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“…In such patients, a degree of hyperphagia, impaired satiety, and obsessive food-seeking behavior has been observed (Skorzewska et al 1989). Increased vagal and decreased sympathetic tones induce insulin hypersecretion with insulin and leptin resistance (Lustig et al 2003;Abuzzahab et al 2019) and impair energy expenditure and basal metabolic rate (Holmer et al 2010). These factors are important causes of hypothalamic obesity.…”

Section: Discussionmentioning

confidence: 99%

Laparoscopic Sleeve Gastrectomy on Severe Obesity after Intracranial Germinoma Treatment: A Case Report

Nezu

Kudo

Ono

et al. 2019

Tohoku J. Exp. Med.

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Hypothalamic obesity is a clinical syndrome characterized by severe and refractory obesity that is caused by hypothalamic function impairment. Recently, bariatric surgery has been attempted for patients with hypothalamic obesity after craniopharyngioma, but experiences have not yet been accumulated in other hypothalamic disorders. Here, we report the case of a 39-year-old male patient with panhypopituitarism who received laparoscopic sleeve gastrectomy (LSG) after intracranial germinoma treatment. The patient was diagnosed with intracranial germinoma at age 15 and achieved complete remission after radiotherapy (total 50 Gy). He was obese during diagnosis [body mass index (BMI), 29.2 kg/m 2 ], and his obesity gradually worsened after the intracranial germinoma treatment, and LSG was considered when his BMI was 48.6 kg/m 2. After 1 month of hospitalized diet-exercise program, LSG was performed. After LSG, his BMI gradually decreased and reached 38.8 kg/m 2 on the day of discharge (6 weeks after the surgery). Five months after LSG, his insulin resistance improved, but insulin hypersecretion remained. Fifteen months after the surgery, his BMI was 31.2 kg/m 2 , with marked decrease in visceral and subcutaneous fat areas (from 393.8 cm 2 and 168.2 cm 2 before the surgery to 111.5 cm 2 and 56.3 cm 2 , respectively.). To our knowledge, this is the first case of LSG for hypothalamic obesity after intracranial germinoma treatment. Although the pathophysiology of hypothalamic obesity is different from that of primary obesity, LSG could be a successful therapeutic choice for patients with hypothalamic obesity after the intracranial germinoma treatment.

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Hypothalamic Obesity: Prologue and Promise

Cited by 53 publications

References 64 publications

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight

A phase 3 randomized clinical trial using a once‐weekly glucagon‐like peptide‐1 receptor agonist in adolescents and young adults with hypothalamic obesity

Laparoscopic Sleeve Gastrectomy on Severe Obesity after Intracranial Germinoma Treatment: A Case Report

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