Olivia Farr

• PhD
• Instructor at Harvard Medical School/Beth Israel Deaconess Medical Center

Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebocontrolled, double-blind trial with 48 obese participants and used funct...

Aims/hypothesis: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide admin...

There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insu...

Context Leptin is a key regulator of energy intake and expenditure. Individuals with congenital leptin deficiency demonstrate structural and functional brain changes when given leptin. However, whether acquired leptin deficiency may operate similarly is unclear. Objective We set out to determine whether the brains of individuals with acquired lept...

Obesity has been associated with altered cerebral functions including cognitive control. The stop signal task (SST) has been widely used to study cognitive control by producing high conflict stop trials among many low conflict go trials. Contrasting these stop trials with go trials provides a measure of saliency processing and response inhibition....

Background Medications leveraging the leptin, PCSK9, ANGPTL3 and FABP4 pathways are being developed for the treatment of insulin resistance and/or lipid disorders. To evaluate whether these pathways are independent from each other, we assessed the levels of PCSK9, ANGPTL3 and FABP4, in normal subjects and subjects exhibiting HIV and highly active a...

Background Diet soda consumption has frequently been linked to obesity and its comorbidities in epidemiological studies. Whether this link is causal and a potential mechanism remains to be determined. Aim/Methods This randomized, cross-over, controlled pilot study sought to determine whether there may be changes in reward-related brain activations...

Leptin has emerged over the past 2 decades as a key hormone secreted by adipose tissue that conveys information on energy stores. Leptin is considered an important regulator of both neuroendocrine function and energy homeostasis. Numerous studies (mainly preclinical and much less in humans) have investigated the mechanisms of leptin’s actions both...

Background&Aims To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences. Methods In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participate...

Postprandial increases in gastrointestinal hormones are associated with reduced energy intake, partially through direct effects on the brain. However, it remains unknown whether the fasting levels of gastrointestinal hormones are associated with altered brain activity in response to visual food stimuli. We therefore performed a whole‐brain regressi...

Based on studies in mice, leptin was expected to decrease body weight in obese individuals. However, the majority of the obese are hyperleptinemic and do not respond to leptin treatment, suggesting the presence of leptin tolerance and questioning the role of leptin as regulator of energy balance in humans. We thus performed detailed novel measureme...

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor (IGF) axis, are altered in maternal plasma in the setting of pre...

Objective: Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment wi...

Background: A newborn's birth weight for gestational age provides important insights into his or her fetal growth and well-being. While the underlying mechanisms regulating fetal growth remain to be fully elucidated, the IGF axis plays an important role. Some components of this axis have been well-characterized in umbilical cord blood, but others...

Aims GLP‐1 analogs have recently risen to the forefront as effective medications for lowering weight through actions in the central nervous system (CNS). However, their actions in the CNS have not yet been studied in the human brain after longer‐term administration at the highest dose approved for obesity (liraglutide 3.0 mg). Materials and Method...

Incretins have risen to the forefront of therapies for obesity and related metabolic complications, primarily because of their efficacy and relatively few side effects. Importantly, their efficacy in altering energy balance and decreasing body weight is apparently through actions in the central nervous system (CNS); the latter may have implications...

Aims To assess the effects of walnuts on cardiometabolic outcomes in obese subjects and to explore underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic, and microbiome analysis integrated with lipid particle fractionation, appetite‐regulating hormones and hemodynamic measurements. Materials and Methods 10 obese subj...

It remains unknown whether leptin regulates body weight in humans and whether this occurs through actions centrally and/or peripherally i.e. by altering hormone and sympathetic nervous system (SNS) activity in humans as it has been suggested by experiments in rodents. We explored body weight and body composition changes in response to short and lon...

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin‐induced improvements in cardiometabolic health remains to be clar...

Obesity is a chronic disease with a continuously rising prevalence that currently affects more than half a billion people worldwide. Energy balance and appetite are highly regulated via central and peripheral mechanisms, and weight loss triggers a homeostatic response leading to weight regain. Lifestyle and behavioral modifications are the cornerst...

The discovery of leptin, an adipocyte secreted hormone, set the stage for unraveling the mechanisms dictating energy homeostasis, revealing adipose tissue as an endocrine system that regulates appetite and body weight. Fluctuating leptin levels provide molecular signals to the brain regarding available energy reserves modulating energy homeostasis...

A better understanding of the underlying pathophysiology of obesity and its comorbidities is needed to develop more effective therapeutics. Although several studies have observed differences in CNS activation/deactivation patterns between obese and lean individuals when viewing food cues, few studies have examined whether the same holds true among...

Objective: Insulin resistance is a major risk factor for type 2 diabetes. ApolipoproteinJ (ApoJ) has been implicated in altered pathophysiologic states including cardiovascular and Alzheimer's disease. However, the function of ApoJ in regulation of glucose homeostasis remains unclear. This study sought to determine whether serum ApoJ levels are as...

Obesity is a complex disease with many causal factors, associated with multiple comorbidities that contribute to significant morbidity and mortality. It is a highly prevalent disease that poses an enormous health and economic burden to society. This article reviews the mechanisms of obesity and its related comorbidities.

Aims: The use of walnuts is recommended for obesity and type 2 diabetes, although the mechanisms through which walnuts may improve appetite and/or glycemic control remain largely unknown. Materials and methods: To determine whether short-term walnut consumption could alter the neural control of appetite using functional magnetic resonance imagin...

Purpose Obstructive sleep apnea (OSA), typically manifested as snoring, is closely associated with obesity. However, the directionality of associations of OSA with cardiometabolic risk markers is unclear, as obesity increases risk for OSA, and OSA results in excess weight gain and its metabolic consequences. Less is known about how obesity and OSA...

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It remains unknown whether obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate altered activation of brain centers in response to food cues. We examined obese prediabetics (n=26) vs obese nondiabetics (n=11) using fMRI. We also performed regression analyses on the basis of the number of MetS components pe...

Background: Methylphenidate (MPH) influences catecholaminergic signaling. Extant work examined the effects of MPH on the neural circuits of attention and cognitive control, but few studies have investigated the effect of MPH on the brain's resting-state functional connectivity (rsFC). Methods: In this observational study, we compared rsFC of a grou...

Patients with type 2 diabetes present an increased risk of bone fractures. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) which has been demonstrated to successfully control glucose levels and promote weight loss without increasing risk of fractures. Recent experimental data indicate that GLP-1 may regulate bone turnover, bu...

Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of intravenous (IV) vs. oral lipids on key molecules regulating energy homeost...

Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling a...

To adapt flexibly to a rapidly changing environment, humans must anticipate conflict and respond to surprising, unexpected events. To this end, the brain estimates upcoming conflict on the basis of prior experience and computes unsigned prediction error (UPE). Although much work implicates catecholamines in cognitive control, little is known about...

To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. The discovery of leptin in 1994 built the foundation for understanding the pathophysiology...

Posttraumatic stress disorder (PTSD) is a growing public health concern. More recently, evidence has indicated that PTSD leads to obesity and associated metabolic dysfunction. Possible mechanisms of this link are through dysfunction of the hypothalamic-pituitary-adrenal axis and related moderation of appetite hormones and neural activity, leading t...

By blocking dopamine and norepinephrine transporters, methylphenidate affects cognitive performance and regional brain activation in healthy individuals as well as those with neuropsychiatric disorders. Resting-state connectivity evaluates the functional integrity of a network of brain regions. Here, we examined how methylphenidate effects resting-...

Detection of a salient stimulus is critical to cognitive functioning. A stimulus is salient when it appears infrequently, carries high motivational value, and/or when it dictates changes in behavior. Individuals with neurological conditions that implicate altered catecholaminergic signaling, such as those with attention deficit hyperactivity disord...

Neuroimaging studies show a correlation between activity of the ventromedial prefrontal cortex (vmPFC) and skin conductance measurements. However, little is known whether this brain region plays a causal role in regulating physiological arousal. To address this question, we employed Granger causality analysis (GCA) to establish causality between ce...

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associat...

Alcohol use and misuse is known to involve structural brain changes. Numerous imaging studies have examined changes in gray matter (GM) volumes in dependent drinkers, but there is little information on whether non-dependent drinking is associated with structural changes and whether these changes are related to psychological factors-such as alcohol...

Conflict detection and subsequent behavioral adjustment are critical to daily life, and how this process is controlled has been increasingly of interest. A medial cortical region which includes the anterior cingulate cortex (ACC) has been theorized to act as a conflict detector that can direct prefrontal activity for behavioral adjustments. This co...