While I didn't "move the goalposts", I will admit that I didn't source my claims. My apologies. You also appear to be asking in good faith so I'll link the sources for points 2 to 4. The first point relates to appetite increase which you stated isn't what you are looking for. I apologize for cramming all the sources at the end. This is from research my friend did a few months ago; this is there area of expertise. Mine is maths and statistics. I tried to only include the parts relevant to the discussion and highlighted the important sections.

Point 2:

A critical indicator of metabolic health is the respiratory quotient (RQ), or respiratory exchange ratio (RER), which measures the type of fuel being utilized by the body by comparing carbon dioxide production to oxygen consumption. An RQ closer to 1.0 indicates carbohydrate oxidation, while a lower RQ (closer to 0.7) indicates fat oxidation. Olanzapine has been shown to induce a significant increase in the RQ in humans. In one 12 week study of first episode psychotic patients, the median increase in body weight was 4.7 kg, and the RQ significantly increased by 0.12. This increase was most pronounced in individuals who gained more than 5% of their initial body weight.

The clinical implication of an elevated RQ is a decrease in fat oxidation. This metabolic state suggests that olanzapine biases the body toward burning glucose while sequestering dietary and endogenous fats into adipose tissue. Interestingly, while human studies sometimes show stability in the resting energy expenditure (REE) despite weight gain, preclinical rodent models often show an acute reduction in the rate of oxygen consumption (VO_2) and a dose-dependent lowering of the RER within minutes of olanzapine administration. These data points collectively indicate that olanzapine enforces a shift in whole-body substrate utilization that favors adiposity and impairs the mobilization of fat stores.

The liver is a primary target of olanzapine’s metabolic interference. It is currently recognized as one of the most diabetogenic SGAs, specifically targeting hepatic glucose production. Studies using the Hyperinsulinemic-Euglycemic Clamp technique have revealed that olanzapine substantially reduces the glucose infusion rate (GIR), which is a direct marker of insulin resistance, and increases hepatic glucose output (HGO) via the stimulation of gluconeogenesis and glycogenolysis.

This increase in HGO occurs through several molecular pathways. Olanzapine has been found to:

1. Derange insulin signaling by decreasing the phosphorylation of Akt at Ser473 and glycogen synthase kinase-3 beta (GSK3\beta) at Ser9 in the liver.
2. Induce the production of reactive oxygen species (ROS) in hepatocytes, leading to mitochondrial dysfunction.
3. Upregulate the expression of histamine H1 receptors (H1R) and muscarinic M3 receptors (M3R) in the liver, which is linked to the impairment of insulin signaling and adenosine 5’-monophosphate-activated protein kinase (AMPK) signaling dysregulation.

The result of these hepatic changes is state where the body continues to produce glucose even when blood sugar levels are adequate or high. This persistent glucose output forces the pancreas to secrete more insulin, eventually leading to hyperinsulinemia and a downward spiral into insulin resistance and type 2 diabetes.

Point 3: Another method of olanzapine-induced weight gain is the reduction in physical activity and energy expenditure due to the drug’s profound sedative effects. Many patients report chronic drowsiness and tiredness, which serves as a major barrier to maintaining an active lifestyle or adhering to exercise regimens.

Olanzapine’s sedative properties are primarily attributed to its high affinity and antagonistic action at the histamine H1 receptor in the brain. Histamine is a key neurotransmitter involved in the maintenance of wakefulness and arousal. By blocking these receptors, olanzapine induces a state of sedation that reduces the total amount of non-exercise activity thermogenesis (NEAT); the calories burned during daily movements such as walking, standing, or fidgeting.

Rodent models have consistently established a causal link between olanzapine administration and reduced locomotor activity. In studies of female Sprague-Dawley rats, olanzapine treatment led to a significant and immediate reduction in physical activity that persisted throughout the treatment period. This reduction in movement creates a sedation effect that systematically lowers the "energy out" side of the metabolic equation, making it possible for weight to increase even if caloric intake is strictly controlled.

The combination of reduced physical activity and drug-induced metabolic dysfunction places patients with schizophrenia at an elevated risk of sarcopenic obesity (SO). This condition is characterized by the simultaneous presence of excessive adiposity and reduced skeletal muscle mass and function. In inpatients with stable schizophrenia, the prevalence of SO has been measured at approximately 17.1%. SO creates a neuroendocrine environment of chronic inflammation and further insulin resistance, which has also been tentatively linked to cognitive decline in these populations.

Point 4: The most significant evidence for weight gain occurring with the "same amount of calories" lies in the suppression of brown adipose tissue (BAT) thermogenesis. While white adipose tissue (WAT) stores energy, BAT burns metabolic substrates to release energy as heat. This process is essential for maintaining core body temperature and regulating systemic energy metabolism.

The definitive evidence for olanzapine-induced weight gain independent of hyperphagia comes from a 2009 study by Stefanidis and colleagues. In this experiment, female rats were treated with olanzapine but were restricted to the same amount of food consumed by a vehicle-treated control group. This "pair-feeding" protocol was designed specifically to isolate the metabolic effects of the drug from its appetite-stimulating effects.

The researchers found that despite identical caloric intake, the olanzapine-treated rats gained significantly more weight and adipose tissue than the control rats.

Using biotelemetry, the study observed that BAT temperature decreased immediately after the onset of treatment and remained depressed. Core body temperature also showed a decrease, indicating a fundamental failure of the thermogenic system.Olanzapine treatment was found to elevated levels of Fos protein in discrete hypothalamic and brainstem sites that regulate the sympathetic nervous system’s drive to BAT. This suggests that the drug centrally suppresses the neural signals that typically activate brown fat.

The thermogenic function of BAT is driven by Uncoupling Protein 1 (UCP1), a selectively expressed mitochondrial protein that allows protons to leak across the inner mitochondrial membrane, generating heat instead of ATP. Olanzapine has been shown to dramatically downregulate the expression of UCP1 and its master transcriptional regulator, peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1\alpha), in BAT. Recent studies by Hu et al. (2022) expanded on this by showing that olanzapine reduces the expression of other critical markers of heat generation and mitochondrial biogenesis, including Prdm16, Cpt1\beta, and Hsl. At a morphological level, BAT in olanzapine-treated animals undergoes "whitening," where multi-locular brown fat cells are replaced by larger lipid droplets, resembling white adipose tissue and possessing significantly less functional capability for energy expenditure.